Introduction

Welcome, Vitalians!

We’re excited to introduce the VitaDAO Longevity Newsletter - your regular update on everything happening across the VitaDAO ecosystem and the wider longevity community.

In each edition, we’ll share highlights from across the DAO - including portfolio updates, progress from our in-house venture studio VitaLabs, insights from our longevity preprint journal The Longevist, and other initiatives taking shape behind the scenes.

We’ll also bring you the most interesting developments from the broader longevity field, from new discoveries in the scientific literature to emerging therapeutic approaches that could shape the future of healthy aging.

Whether it’s new science, new ventures, or new ideas, this newsletter is designed to keep the VitaDAO community informed and connected.

Let’s dive in.

VitaDAO Portfolio Highlights

To date we have funded more than 30 projects. We are always looking out for more ground-breaking longevity drug discovery science to support, so email us at discovery@vitadao.com if you have, or know any researchers with, a great translational idea in need of funding!

Aubr.ai — AI BioAgent co-developed with Bio Protocol and LEV Foundation to accelerate longevity research and support the RMR2 combination rejuvenation study in mice

Aubr.ai, a pioneering AI BioAgent trained on Dr. Aubrey de Grey’s research insights and integrated with DeSci funding tools, continues to grow its community interactions — try it at aubr.ai or @Aubrai_.

Aubr.ai is now the state-of-the-art AI for longevity research. Trained on decades of aging literature, private lab notes, and insights from Dr. Aubrey de Grey’s lab, Aubrai is ranked #1 on BixBench — scoring 48.78% open-answer, 55.12% multiple-choice + refusal, and 64.39% multiple-choice — outperforming Edison Scientific and Kepler. The agent runs up to 8 hours of autonomous deep research on aging questions, with persistent memory so longevity insights compound across sessions, covering literature synthesis, hypothesis generation, and lifespan experiment design.

On the research side, RMR2 pilot studies are now underway at LEV Foundation, building on RMR1 learnings by testing a larger set of at least 8 combination damage-repair interventions (vs. 4 in RMR1) with rapamycin as baseline across all groups; the main phase is expected to begin around mid-2026 with significant results by 2028.

Our long-term vision is to autonomise and scale the discovery of longevity therapeutics. Aubrai, who has been trained on decades of longevity literature, has already begun generating novel hypotheses, resulting in a growing pipeline of ideas ready for experimental validation. Watch this space!

FOXO3 – Developing antisense oligonucleotide therapeutics targeting FOXO3 isoform expression for degenerative disc disease.

The project has made strong early progress in Q1 2026, completing oligo design across three distinct mechanisms of action using clinically validated chemistry. All primary cell lines (dermal fibroblasts, annulus fibrosus, and nucleus pulposus) have been procured and expanded, with preliminary data confirming successful intracellular delivery in disease-relevant cell types. The team is now characterizing baseline isoform expression and assessing oligo functionality, running ahead of the milestone 1 timeline.

To learn more about ASO drug discovery, check out this recent review: Antisense Oligonucleotide Therapeutics Targeting Age-Related Diseases.

Rapamycin & Exercise Trial – Double-blind, placebo-controlled trial of weekly rapamycin combined with exercise in older adults.

The manuscript reporting results from the completed 40-participant trial has been accepted for publication by the Journal of Cachexia, Sarcopenia and Muscle. Full results will be publicly available upon publication.

Reversing Periodontal Disease — Testing small molecule inhibitors of the PI3K/NF-κB/mTOR pathway against age-related gum disease and bone loss in aged mice

The project is now complete. Prof. Jonathan An’s team at the University of Washington showed that aging upregulates PI3K/CSF1R signaling in periodontal tissues, driving chronic inflammation and bone loss, and that pathway-specific inhibition with three small molecules modulates RANKL, NF-κB signaling, and inflammatory cascades, with structural analysis demonstrating attenuation of alveolar bone loss. The team presented results to the community (watch here) and a manuscript is in preparation for a peer-reviewed journal.

Transfidelity – Developing small molecule therapeutics that improve protein biosynthesis accuracy to combat age-related neurodegenerative diseases.

The project has reached a key inflection point, with data across multiple assay systems demonstrating that lead compounds restore cellular proteostasis and significantly reduce protein aggregation — including in disease-relevant patient-derived cell models. Phosphoproteomics analysis has identified the specific signaling pathway and downstream target through which the compounds act, opening a clear route for novel IP generation and future drug design.

VitaDAO will soon be launching its own senescence target discovery project - VitaSeno. To learn more about senolytics as a therapy, check out this interesting review to learn more: Cellular senescence as a therapeutic target for aging intervention.

VitaLabs - our in-house Longevity Venture Studio

This is the last week to apply for VitaLabs Season 2. We have received 94 applications so far, spanning the Americas, Europe, Asia, Africa, and the Middle East. The ideas coming in range from therapeutic moonshots (senolytics, proteostasis, mitochondrial interventions) to diagnostics and biomarkers (including liquid-biopsy concepts), plus AI-first computational platforms and DeSci-native infrastructure.

We built Season 2 of VitaLabs around a simple premise: information is only valuable if it can change a decision. So, we design projects to answer one essential question early: is this idea worth scaling into a bigger program? In practice, this means starting with the smallest decisive test—a fast, interpretable experiment designed to resolve the highest‑leverage uncertainty first, with a clean line‑of‑sight to human relevance.

Since we don’t expect applicants to already work in this style, we’re running a more interactive application process this season. With the help of Aubr.ai, our longevity research agent, some applicants will receive a short revision email with high-yield questions that help tighten the proposal: fill in what is missing, surface the biggest unknowns, and make the first experiment easier to evaluate and execute. But it is not just “feedback.” It is also a small taste of the fellowship itself. The questions are written in the VitaLabs style, so applicants can see how we pressure-test an idea, clarify what really matters, and turn a promising concept into a lean, decisive experimental plan.

Fellows receive dedicated research funding, plus hands-on support. Experimental work can be executed via cloud labs or CROs, and Fellows get full access to Aubr.ai. Apply Today

News and media

We will now shift gears to highlight what has been happening in the wider longevity ecosystem.

One of the most significant pieces of longevity news this month is that David Sinclair’s company Life Biosciences has been given the go-ahead for a clinical trial to test if partial epigenetic reprogramming can rejuvenate cells in the eye to restore vision loss. This will mark the first partial reprogramming human trial.

More positive signs are also on the horizon for longevity therapeutics as ARPA-H pours millions into healthspan-focused human trials and FDA rewrites drug approval rules and longevity stands to gain.

And it’s not just humans who are getting closer to longevity therapeutics, as loyal raises $100m as canine longevity drug nears approval.

Nature has already solved a number of age-related issues that affect humans, for example, the human thymus starts losing mass and functionality not long after adulthood, whereas this month we learned that axolotls can completely rebuild their thymus and they also retain fertility throughout lifespan. For more on comparative biology, check out this article on What the World’s Longest-Lived Animals Can Teach Us About Aging.

There is also a lot we can learn from long-lived humans as this interesting article highlights how centenarians’ blood sheds light on the mechanisms of longevity

Until we can harness all of the secrets of long-lived humans and other organisms, there are simple lifestyle alterations we can make straight away. One of the simplest longevity interventions we can introduce into our lifestyle is eating a healthy diet. The USDA just released Dietary Guidelines for Americans, 2025–2030 and their message is simple: eat real food! Along with a healthy diet, there are many other lifestyle improvements to be made at any age, see: Five healthy habits for longevity in your 40s and 50s.

Some people like to take their longevity protocols even further, check out this article discussing why people are spending $1,300 on longevity treatments, and also meet the Vitalists: the hardcore longevity enthusiasts who believe death is “wrong”. However, one should always apply caution before trying anything that has not been rigorously tested, for example we learn this month that a popular brain supplement is linked to shorter lifespan in men. And more bad news for those harbouring a Y chromosome: Men Lose Their Y Chromosome With Age. We Finally Know The Cost.

For the podcast fans amongst you, Charles Brenner appeared on Rhonda Patrick’s Found my Fitness, and stated that her questions were probably the best he has been asked on a podcast. Check it out to learn more about NAD+ and the science behind it: How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging | Dr. Charles Brenner.

Another interesting podcast to check out is Eleanor Sheekey discussing the preprint “A Minimal Model Explains Aging Regimes and Guides Intervention Strategies”, delving into why so many anti-aging drugs work in mice but fail in humans? It turns out, we might be aging in fundamentally different ways. A new “minimal model” from physicists Peter Fedichev and Jan Gruber suggests that aging isn’t a chaotic mess of billions of problems, but a process governed by just three macroscopic variables. Watch the Sheekey Science show discuss the 3 levels of aging therapeutics.

Preprint Corner - in collaboration with

The Longevist is a preprint overlay journal spotlighting the most promising longevity studies each quarter.

Preprints have revolutionised scientific publishing by enabling researchers to share their discoveries with the world immediately. However, the vast number of preprints being published on a daily basis makes it extremely challenging to keep up with all the latest literature. To assist with this, VitaDAO launched - The Longevist - a longevity-focused preprint overlay journal, curated by key opinion leaders from academia and industry. These experts used on-chain voting to highlight the most significant longevity research preprints each quarter, offering a novel way to spotlight promising studies way ahead of their publication in traditional journals.

We have temporarily paused new editions of The Longevist whilst we build something new.

Moving forward, we aim to further empower our readers by increasing the frequency of our curation and providing tools that make scientific literature easier to analyze and understand. To achieve this, we will be transitioning to fully automated curation by developing our bespoke Longevist AI Agent (LAIA), designed to autonomously curate and analyze the most groundbreaking longevity preprints.

LAIA will curate a daily stream of longevity preprints which will be posted to The Longevist website and VitaDAO’s communication platforms (Discord & Telegram). LAIA will also be deployed on these platforms to answer scientific questions, making complex literature more accessible to community members of all levels of scientific understanding, while keeping them immediately abreast of the latest discoveries.

To stay updated on The Longevist and LAIA, please sign up to our newsletter and follow us on X.

To whet your appetite, here are some recent preprints for you to delve into:

LongevityBench: Are SotA LLMs ready for aging research?

Researchers created LongevityBench, a test suite to evaluate whether AI models truly understand aging biology and can use biological data to predict health outcomes and lifespan. The benchmark reveals current AI weaknesses and suggests ways to improve their usefulness in longevity research.

Codon bias coevolves with longevity

Long-lived mammals appear to have evolved genetic “spellings” that reduce harmful mutations and help proteins fold correctly, lowering the buildup of damaged or misfolded proteins linked to aging. These subtle changes in DNA coding may improve cellular stability over time, contributing to longer lifespans.

Maximal human lifespan in light of a mechanistic model of aging

Human maximum lifespan has changed little because it is mainly determined by how fast cellular damage accumulates and how well the body can repair or remove it. Healthy lifestyles can help people live longer on average, but meaningfully extending the absolute human lifespan will likely require therapies that directly reduce or repair biological damage.

Rare longevity-associated variants, including a reduced-function mutation in cGAS, identified in multigenerational long-lived families

Longevity can run in families partly due to rare genetic variants that reduce inflammation and slow cellular aging. One such variant weakens the cGAS-STING immune pathway, which may delay age-related damage and help people live longer, healthier lives.

On Using Large Language Models to Understand the Language of Life

Advances in AI and large biological datasets could eventually allow scientists to build predictive models of how human cells, tissues, and organs function over time. Such models could transform medicine by helping us understand, predict, and treat diseases more effectively, though this goal remains technically challenging.

Why we age: the four process model

The authors propose that aging is driven not simply by accumulated damage but by a built-in biological process that slows cell metabolism to prevent runaway cell growth, such as cancer. This protective slowdown may unintentionally lead to insulin resistance, weight gain, inflammation, and other age-related diseases, offering a unified explanation for why we age.

SenCat: Cataloging human cell senescence through multiomic profiling of multiple senescent primary cell types

Scientists created a comprehensive catalog of aging (senescent) cells across many human cell types, showing there is no single universal marker but shared stress and repair pathways. This resource could help researchers better identify and target harmful senescent cells in different tissues to treat age-related diseases.

Integrating AI and causal genetics to prioritize therapeutic targets for aging and age-related diseases

Researchers used AI to analyze large biological datasets and identify shared molecular targets linking aging with multiple age-related diseases, highlighting chronic inflammation as a central driver. Their findings point to existing drug targets — such as IL6 and NLRP3 pathways — that could potentially be repurposed to treat several aging-related conditions at once.

Published Literature Hot picks

Cellular survivorship bias as a mechanistic driver of muscle stem cell aging

Study of the allocation of resources to survival over reproduction in stem cells during aging. As we age, muscle stem cells become slower to repair damage because they shift toward survival mode, producing more NDRG1, which dampens growth signals needed for rapid regeneration. This reflects a trade-off: cells last longer but respond less effectively to injury, contributing to slower muscle healing in older individuals. Also short commentary here: Scientists reverse muscle aging in mice and discover a surprising catch.

Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging

Scientists created a detailed map of how gene regulation changes with age across many mouse tissues, revealing shifts in cell types and DNA accessibility, especially in immune cells. The study also found important sex-specific differences, highlighting the need to consider biological diversity when studying aging.

Senotoxins target senescence via lipid binding specificity, ion imbalance and lipidome remodeling

Scientists discovered that a toxin called sticholysin I can selectively kill senescent (“aged”) cancer cells that remain after chemotherapy and can promote relapse. In mice, combining this toxin with chemotherapy improved tumor remission, suggesting a new strategy to make cancer treatments more effective.

Comparative analysis of senolytic drugs reveals mitochondrial determinants of efficacy and resistance

Scientists compared 21 “senolytic” drugs that aim to clear aged, damaged cells and found two of the most effective, though some stubborn cells survived by maintaining healthy mitochondria. Increasing metabolic stress — through approaches like ketogenic diets or certain diabetes drugs — made these treatments work better in lab and mouse studies, suggesting combination strategies could improve therapies for aging and cancer.

A decline in glycolytic ATP production is the fundamental mechanism limiting lifespan; species with an optimal rate of decline over time survived

As we age, our cells produce less quick energy through glycolysis, which may contribute to slower cell repair and other signs of aging. The authors propose this slowdown evolved to help species survive food scarcity and balance reproduction, potentially explaining why lifespans are limited and why cancer cells or certain animals maintain unusually long or “immortal” cellular activity.

Association between vitamin intake and biological aging: evidence from NHANES 2007–2018

In a large U.S. study, people who consumed more vitamins — especially vitamin C — showed signs of slower biological aging based on physiological markers. The findings suggest that a vitamin-rich diet may help promote healthier aging, with particularly strong benefits in men and those with existing health conditions.

The human pathome shows sex and tissue specific aging patterns

By analyzing millions of pathology reports, researchers identified patterns showing when aging begins in different tissues and found that women tend to start aging earlier but more slowly, while men age later but faster. Using these insights, they highlighted an existing drug, nintedanib, as a potential anti-aging therapy, showing it reduced cellular aging markers and extended lifespan in fruit flies.

Astronauts as a Human Aging Model: Epigenetic Age Responses to Space Exposure

A short space mission caused astronauts’ biological age markers to rise by nearly two years within a week, likely due to stressors like microgravity and radiation. Encouragingly, these changes reversed after returning to Earth, suggesting spaceflight can temporarily accelerate aging but also offers a unique way to study and test anti-aging strategies.

Partial Reprogramming Is Conserved from Insect to Mammal

Aging is partly driven by the buildup of damaged cells and the decline of stem cells, but research shows that mature cells can be partially “reprogrammed” to a more youthful state using Yamanaka factors. Along with senolytic drugs and aging clocks, this approach could open new ways to extend lifespan and improve health in later life.

Lifespan-Extending Endogenous Metabolites

Certain naturally occurring metabolites help regulate how the body senses nutrients and controls genes linked to aging, and some can extend lifespan in model organisms. Targeting these metabolic pathways may offer a way to slow aging and improve healthspan, though proving effectiveness and safety in humans remains a challenge.

The ethics case for longevity science

The authors argue that extending healthy lifespan is not just beneficial but ethically justified, emphasizing personal autonomy and the intrinsic value of life. They contend that common concerns — such as overpopulation, inequality, or loss of meaning — are not strong reasons to oppose longevity research and that preventing age-related suffering should be the moral priority.

The pursuit of understanding human longevity

Living past 100 does not necessarily mean living in poor health; studies show that exceptional longevity is linked to resilience shaped by genetics, efficient metabolism, low inflammation, and healthy lifestyles. Research on centenarians and Blue Zone populations suggests that long, healthy lives result from a combination of biological traits, environment, and daily habits working together.

And a final few papers that you might find of interest:

• Select Small Non-Coding RNAs Are Determinants of Survival in Older Adults

• Senolytic‐Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers

• CardioMetAge estimates cardiometabolic aging and predicts disease outcomes

• Plasma-based strategies for systemic rejuvenation: critical perspectives on clinical translation

• Polyamine metabolism as a regulator of cellular and organismal aging

Outro

We hope you enjoyed this month’s update on the latest happenings at VitaDAO and across the wider community. Stay tuned for more on what we’ve been working on in next month’s edition.

AUBRAI is an on-chain AI agent accelerating longevity research. Built with Dr. Aubrey de Grey's expertise, it synthesizes papers, critiques study designs, and shares live updates about RMR2.

At the heart of AUBRAI's mission lies the Robust Mouse Rejuvenation (RMR2) project - an ambitious study to double the remaining lifespan of middle-aged mice. If successful, it could be aging's 'AlphaFold moment': a proof that multi-target rejuvenation works and is worth scaling.

The $100K Hypothesis Challenge

Calling all researchers!

► Use @Aubrai_ to create and refine a longevity hypothesis

► Best hypotheses are selected by @aubreydegrey and qualify for up to $100K in funding

► 20K $BIO bounty for referring researchers whose hypotheses get selected

How it works

• Researchers worldwide can use Aubrai as a researcher co-pilot to fine-tune novel hypotheses about longevity - eg, a new clinical treatment or biological mechanism.

• Submit a research proposal in the form below

• Aubrey de Grey will select the top hypotheses, making them eligible for up to $100K in milestone-based research funding.

• Funding comes from IP-Token “Ignition Sales” on the Bio Launchpad & VitaLabs, VitaDAO’s incubation program for scientists pioneering high-risk, high-reward longevity research, turning ideas into IPTs and biotech spinouts through a community-driven funding model.

$BIO Bounty

Know someone who might be interested in submitting a research proposal? They could be students, medical professionals or independent researchers.

Submit research proposal here.

VItaDAO developed Aubrai with the help of Bio Protocol. Aubrai is trained on the unpublished lab data of longevity scientist Aubrey de Grey as well as knowledge collected from researchers worldwide via social media, messaging platforms and the Aubrai terminal.

As an onchain AI co-scientist, Aubrai can generate and validate hypotheses, design wet-lab experiments and encrypt scientific data, enriching research outputs while protecting trade secrets.

AI-driven biology is experiencing explosive growth, with giants like Google and OpenAI building scientific agents capable of reading papers and generating hypotheses. But these tools remain siloed in Web2 - disconnected from capital, coordination and shared knowledge. Aubrai breaks these barriers by integrating scientific AI with onchain features for data sharing, continuous funding and discovery monetization, directly engaging the global longevity community.

How to Use Aubrai

• You can now prompt Aubrai on X by tagging @Aubrai_. The agent is designed to answer a range of questions - from complex scientific inquiries to general health hacks.

• Valid hypotheses generated by Aubrai are hashed on Base through Molecule's Proof-of-Invention (POI). This creates a blockchain-verified trail of scientific progress, enabling value and recognition from breakthroughs to flow upstream to contributors whose early insights or negative results paved the way for later discoveries.

• View the Aubrai dashboard for tracking hypotheses generated, knowledge ingested, IP-NFTs and other agent analytics. The Aubrai Researcher Terminal is currently in Private Beta, with verified researchers including those with .edu emails getting expedited access. Sign up for Beta access.

Aubrai can utilize funding from $AUBRAI trading fees to bootstrap experiments, and eventually tokenize validated data as onchain knowledge assets known as IP-Tokens.

RMR2 Study

Aubrai is trained on cutting-edge research from Dr. de Grey’s lab, LEV Foundation, including the Robust Mouse Rejuvenation (RMR2) project, a comprehensive study testing rejuvenation therapy combinations to achieve lifespan extension in mice. If successful, it could be aging's "AlphaFold moment": a proof that multi‑target rejuvenation works and is worth scaling.

Findings from the RMR2 study will be fed directly into Aubrai’s knowledge graph, continuously enriching the agent with the latest insights from LEV.

Scaling Longevity Intelligence

Dr. Aubrey de Grey said: “Aubrai represents a radical new way to scale collective scientific intelligence. By fusing my team’s expertise with decentralized AI and the wisdom of the global longevity community, we're creating something unprecedented – a scientific AI agent that doesn't just process information, but actively helps researchers turn discoveries into real-world therapeutics.”

The $AUBRAI Token

Aubrai Contract Address: 0x9d56c29e820Dd13b0580B185d0e0Dc301d27581d

Aubrai on Aerodrome

Aubrai on Coingecko:

Aubrai twitter/x @Aubrai_:

Aubrai on Coindesk: https://www.coindesk.com/markets/2025/08/25/decentralized-science-project-aubrai-launches-on-base-to-tackle-science-funding-s-valley-of-death

Aubrai Website: https://aubr.ai/

Learn more about Aubrai: https://docs.aubr.ai/

ARTAN Bio(VitaRNA) and Syenex just announced a strategic collaboration that could significantly speed up the development of ARTAN-102, a pioneering gene therapy designed to reverse epigenetic changes associated with aging. This partnership brings together ARTAN's innovative codon suppressor platform with Syenex's VivoCell delivery technology.

The Power of Precision Delivery

The collaboration centers on a critical challenge in gene therapy: getting the treatment to the right places in the body. Syenex's VivoCell Platform provides the precision in vivo delivery capabilities that ARTAN needs to move their therapy from laboratory proof-of-concept to IND-enabling studies - the crucial step before human trials can begin.

"Precise, efficient delivery is critical to maximizing the potential of ARTAN-102," explained Dr. Michael Torres, Co-Founder and Chief Scientific Officer of ARTAN Bio. "Syenex's track record in delivery vehicle innovation and manufacturing scale makes them a natural partner as we progress toward IND-enabling studies."

What the Partnership Includes

The collaboration has three main components:

• Rapid Prototyping: ARTAN gains full access to the VivoCell Platform, including extensive libraries of precision delivery components. Syenex will provide pre-clinical scale prototyping and production support, allowing ARTAN to quickly test and refine delivery approaches.

• Manufacturing Scale-Up: Once optimal prototypes are developed, they'll be transferred to Syenex's CDMO (Contract Development and Manufacturing Organization) partners for GMP-grade production - the pharmaceutical quality standard required for clinical trials.

• Flexible Licensing: The agreement includes a non-exclusive program license option for the clinical delivery vehicle composition, giving ARTAN strategic flexibility as they move forward.

About ARTAN-102 and VitaRNA

ARTAN Bio, also known as VitaRNA, is developing first-in-class therapeutics designed to restore full-length, functional proteins that become disrupted during aging and age-related disease. Their lead candidate, ARTAN-102, uses a novel codon suppressor approach to address mutations that accumulate as we age, particularly targeting proteins crucial for tumor suppression, DNA repair, and neurological function.

The VitaRNA project recently released impressive first in vivo data showing ARTAN-102 is safe and reaches multiple tissues in mice. The 14-day study found the therapy successfully reached the liver (350-fold increase), heart (32-fold), lungs (20-fold), brain (4-fold), kidneys (10-fold), and pancreas (12-fold) - all without adverse effects, changes in body weight, or blood cell count alterations.

Jay Rosanelli, CEO of Syenex, emphasized the potential impact: "ARTAN Bio has generated strong preclinical data on the therapeutic potential of their lead drug candidate, ARTAN-102. By combining their codon suppressor platform with our VivoCell Platform, we aim to shorten development timelines and unlock treatment options for aging and age-related disease."

VitaRNA has released first in vivo data showing their lead gene therapy candidate, ARTAN-102, is safe and reaches multiple tissues in mice. The 14-day study marks an important preclinical milestone for one of the first tokenized gene therapy projects.

Led by CEO Anthony Schwartz and CSO Michael Torres - top-tier biotech executives with a proven track record of advancing drug development platforms into human clinical trials - the project has progressed from initial VitaDAO funding ($91k) and registration onchain as an IP-NFT, through a subsequent $300k raised via IP tokenization, to reach several key milestones in developing tRNA suppressors targeting nonsense mutations.

Study Results

The mouse study (n=4 per group) evaluated ARTAN-102 delivered at 1.8×10¹² GC/mouse and found:

• No changes in body weight or blood cell counts

• No adverse events

• Successful delivery to all six tissues examined, with highest expression in liver (350-fold increase), followed by heart (32-fold), lung (20-fold), pancreas (12-fold), kidney (10-fold), and brain (4-fold)

The Science

ARTAN-102 targets arginine nonsense mutations (CGA codons) that accumulate with age and disrupt proteins like p53, ATM, and APP. These mutations contribute to aging and various diseases. The therapy uses AAV9 to deliver genetic suppressors that restore normal protein function.

Supporting research published in Nature Aging (January 2025) shows CpG mutations accumulate over time and correlate with epigenetic aging, validating the therapeutic approach.

Progress Update

• Initial screening identified 2 lead candidates from 15 vectors

• Filed 2 provisional patent applications

• Manufacturing partnership established with Lonza for GMP production

• Currently raising $500k for non-human primate studies

• Targeting $5M total to reach human trials within 12 months

The project has progressed from VitaDAO's initial $91k funding and $300k IPT raise to achieving pharmaceutical-grade manufacturing and safety data.

What This Means

This data demonstrates that DeSci-funded projects can produce legitimate therapeutic candidates. By combining community funding with traditional drug development, VitaRNA has achieved in months what typically takes years in conventional biotech.

Next steps include completing primate toxicology studies and finalizing GMP manufacturing before pursuing first-in-human trials.

Dataroom: https://molecule.xyz/ipts/VITARNA?shareFileDid=did:odf:fed01f889955f203b0d5383ff64fc1c6e1ef6c9b16613925f8edf5effda4e4ef110eb

Learn more: https://vitarna.xyz

Join the community: https://t.me/vitarna

Coingecko: https://www.coingecko.com/en/coins/vitarna

High-Level KPIs*

• Treasury: $42M (411% YoY growth)

• Token Holders: total of 8,500+ across all blockchains (250% YoY growth)

• Re-org success: monthly burn rate dropped 50% from ~$100k to ~$50k

*as of December 2024

Scientific Updates

VitaDAO's projects showed promising developments towards medicines that could slow or reverse aging by reprogramming aged cells, removing toxic aging cells, and treating other age-related conditions:

• AB4AD - Successfully identified and validated 31 proteins that showed significant immune response in AD patients or controls. Some of them are preferentially targeted in Alzheimer's patients, while others may show a stronger reaction in old cognitively-intact individuals.

• Etheros Pharma in-vivo testing confirmed a large therapeutic window for their lead molecule, and has succeeded in creating a number of new compounds for potential new applications.

• The Exercise & Rapamycin clinical trial co-funded by VitaDAO under the leadership of Dr Stanfield has completed the data collection phase. Data analysis will start shortly and results should be published in a few months. Protocol available here.

• Mantis Photonics tested their hyperspectral ocular imaging technology in a small clinical trial with 57 people, obtaining 93% accuracy in diagnosing Alzheimer’s. These results will be published soon.

• Oisin Bio published a paper on the safe and effective in vivo delivery of DNA and RNA using their proteolipid vehicles in collaboration with Entos.

• Remedium Bio published preclinical data demonstrating the performance of its adjustable dose gene therapy platform – Prometheus™ in a paper on the Gene journal.

• Vita-FAST went through two iterations of lead series reaching nanomolar potency at inducing autophagy.

• VitaRNA successfully identified from a series of candidate oligos a promising lead oligo and validated it in combination with an AAV. The project is currently raising $1M in a follow-on crowdsale for drug formulation and testing in animal models.

Business updates

• Cyclarity Therapeutics announced the closing of the first tranche of its Series A funding round, led by Ki Tua Fund LP and Starbloom Primrose LP. They will use the funds to commence clinical trials or the development of UDP-003, a novel therapeutic designed to reduce atherosclerotic plaque accumulation.

• HDAX Therapeutics raised a $3.2M seed round for developing HDAC6 inhibitors with blood-brain barrier penetration capabilities.

• The Longevity Hackers Movie co-funded by VitaDAO has completed production and is now available in VOD on Apple TV, Prime Video, Google Play, Vudu, and soon on Fandango. More information here.

• Oisín Biotechnologies announces the first close of $15 million series A financing round to advance therapies for age-related diseases, with AbbVie ventures leading the round.

• Repair Biotechnologies advanced their Cholesterol Degrading Platform for atherosclerosis treatment, completing CMC work and pre-IND package. They just announced a positive pre-IND Meeting with FDA for their lead REP-0003 to treat homozygous familial hypercholesterolemia.

• Rubedo Life Sciences secured a $40M Series A funding and advances to human trials, developing selective "smart drugs" targeting senescent cells. They also hired a seasoned biotech CEO and expanded in Europe. Finally, the named their clinical candidate at JPM, becoming the second clinical-stage company in VitaDAO’s portfolio.

• Turn Bio signed a $300M+ licensing deal with HanAll Biopharma for eye/ear therapies; reported significant skin cell rejuvenation results at ESDR Conference.

Core Initiatives

VitaLabs

VitaDAO launched VitaLabs in Q4-24, an initiative designed to create an in-house network of interdisciplinary scientists dedicated to pioneering cutting-edge longevity science. Our mission is to radically extend human healthspan and lifespan by developing cutting-edge research while empowering democratic ownership of Intellectual Property through IPTs.

The Fellowship Program, designed to attract top tier talent for the inaugural VitaLabs season received over 70 applications and 12 innovative project submissions. The community has selected four exciting projects to receive support from VitaDAO through a quadratic governance proposal.

1. Unlocking Longevity Through Stem Cell Rejuvenation using single-cell analysis

2. Synthetic Vitality: Synergistic Drug Combinations to aim for Radical Life Extension

3. Lengthening telomeres with hTERT expression-inducing small molecules

4. Targeting the Key Neuroinflammatory Pathway in Brain Aging

Products

VD-001: The first VitaDAO longevity product launched successfully with:

• Thai FDA approval secured

• High-doses of spermidine

• A presentation to industry leaders including CZ Binance and Vitalik Buterin during DeSci Day at the Binance Labs BUIDLer House in Bangkok

What’s Next (Q1-25)

• Compounds from The Longevity Prize will soon be launched on pump.science

• Introduction of expanded product line focusing on innovative longevity formulations

• Supplements pre-order system and official marketplace goes live with exclusive discounts to community members

AI Agents

Our experiments with various agent frameworks have been nothing short of mind-blowing, and we see multiple ways to leverage their capabilities to advance our mission. By integrating AI Agents deeply into our research and operational workflows, we aim to unlock new efficiencies, accelerate discovery, and create novel avenues for collaboration.

• Development of the first DeSci AI agent: Together with BIO, we are developing an AI Agent designed to impersonate Aubrey de Grey providing community members with 1. actionable longevity insights and advice aligned with Aubrey’s well-known reasoning; 2. live updates about the RMR2 study to keep the community informed about the development of the study and 3. growth and excitement through meme creation and shareable content.
  

• Partnership with YNE: We have also been amazed by the latest breakthroughs from the Yes or No Error (YNE) team and are thrilled to announce a new partnership. Initially, the plan is to have YNE publicly auditing research findings from several of our core projects, providing an added layer of transparency and rigor. In the future, we aim to expand this collaboration to include other initiatives such as VitaLabs, ensuring robust real-time verification and accountability across our entire research ecosystem.
  
  

Team expansion

VitaDAO is hiring aggressively to fuel its next stage of growth. Key roles include:

• Longevity Pod Lead

• APAC Lead*

• Web3 BD*

• Marketing Manager

• Community Manager

• Web3 Tech Lead

• AI Lead

*already negotiating terms with selected candidates

If you know of any outstanding candidates or have recommendations within your network, we would greatly appreciate your support and referrals!

We want to express our deepest gratitude for your unwavering support. It has been a remarkable journey filled with both challenges and breakthroughs, and we truly appreciate you standing with us every step of the way. We’re more excited than ever about what lies ahead and look forward to continuing this journey together.

Thank you for being a part of our story!

VitaDAO team

About VitaLabs
VitaLabs is VitaDAO's research program focused on finding new ways to improve health and extend life. It supports researchers with funding, mentorship, and resources to explore bold ideas that could change the way we think about aging​.

Your Vote Matters
The VitaDAO community is now voting to choose four projects to receive:

• Funding to carry out experiments.

• Mentorship from top scientists.

• Resources to help their ideas grow.

This is your chance to support the ideas you believe in! The voting process uses quadratic voting, which gives more weight to projects with broad support. If you hold Vita tokens, you can vote now on the Snapshot platform.

Projects to Vote On

1. Targeting the Key Neuroinflammatory Pathway in Brain Aging

This project seeks to characterize the key gene regulatory programs that drive a healthy aging brain toward pathological changes (such as deposition of senile plaques), especially via age- related neuroinflammation and microglial activation.

2. The Genome Expansion Project

Genome dysregulation is a nearly universal characteristic of aging, largely due to increased transposable elements (TEs) activity. These DNA segments, which can move within the genome, constitute about 50% of our DNA, but aging research often focuses on the less than 1% that are coding regions.

3. Lengthening telomeres with hTERT expression-inducing small molecules

Our team has developed a family of small molecules (analogs) that induce expression of hTERT in human cell lines, which in turn increases the amount and activity of telomerase. This would ideally involve two phases: testing 5 molecules in C. elegans and then mice.

4. Precision medicine for brain health informed by gene-mapped MRI features

The published literature suggests that inter-individual variability in regional brain aging dynamics can be mapped to gene variants, gene network architectures, and gene expression patterns, which can inform personalized interventions for the maintenance of brain health.

5. Unlocking Longevity Through Stem Cell Rejuvenation using single-cell analysis

By leveraging single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and multi-omics data integration, we will systematically study the molecular mechanisms of stem cell aging; and identify novel targets and therapies to enhance their regenerative capacity.

6. Precision Telomere Mapping: Pathways to Longevity and Disease Prevention

Mapping and modulating telomere dynamics across tissues to uncover aging pathways and develop precision therapies for longevity and disease prevention

7. Enzyme engineering for crosslinked collagen turnover in the extracellular matrix

The project postulates extracellular matrix stiffening as the upstream cause of the hallmarks of aging and proposes leveraging generative AI to engineer matrix metalloproteinases capable of degrading sugar-modified, or glycated, collagen that resists normal remodeling.

8. Revive Synergy Longevity Labs – Targeting Aging at Its Roots

Revive Synergy Longevity Labs is dedicated to extending healthspan by addressing cellular aging and systemic inflammation. We integrate AI-powered diagnostics, senolytic therapies, and microbiome interventions to target aging markers.

9. Rewiring Aging: Restoring Gene Networks to Unlock Healthy Longevity

This project develops a computational model to predict biological age and identify mechanisms driving aging through single-sample gene co-expression networks. By analyzing GCN topology, we will identify biomarkers and transcriptional regulators linked to gene coordination loss.

10. SkinDeep: Stable and Transient Endogenous Therapy

The project aims to determine 2 to 5 target inserts for codon optimization and ligation into plasmid vectors for later development of animal cell line viability assay of accumulated therapeutic plant nutraceuticals.

11. “The Renaissance Clinic “ supplement line

Worlds first supplement line backed by numerous research studies with FDA/regulatory body approved health claims.

12. Synthetic Vitality: Synergistic Drug Combinations to aim for Radical Life Extension

This project explores two approaches to radical life extension: GIGA (Get'em Growing Again) and MEGA (Make Genes Express Again). Using "synthetic vitality," we target synergistic drug combinations for greater lifespan impact than traditional methods.

Vote Now
You can help decide which projects get funding and support. If you hold Vita tokens, cast your vote now on Snapshot.

Your vote can make a difference!

In a significant milestone for decentralized science (DeSci), VitaRNA/Artan Bio has announced a $1M fundraise to support their groundbreaking gene therapy program targeting aging-related mutations. This initiative, which began as the first tokenized gene therapy project through VitaDAO, is now preparing for animal studies following successful in vitro validation.

Recent Achievements and Manufacturing Partnership

The company reached a major milestone in October 2024, successfully identifying and validating two promising drug candidates from an initial screening of 15 prototypes. These candidates have demonstrated effective suppression of arginine nonsense mutations in cancer cell lines with P53 mutations, marking a significant step forward in their therapeutic approach.

In a strategic move to ensure highest quality standards, VitaRNA/Artan Bio has established a manufacturing partnership with Lonza, a world-renowned Contract Development and Manufacturing Organization (CDMO). This collaboration has already yielded progress in process development for both plasmid and viral vector manufacturing, with optimization of production yields and purity well underway.

Funding Allocation and Next Steps

The new $1M fundraise will support several key initiatives:

• Scaling up viral vector manufacturing for GLP-toxicology studies

• Development of bioanalytical assays

• Validation of aging-related biomarkers

• Comprehensive safety testing

• Expansion of the IP portfolio

• FDA consultation and regulatory strategy development

Clear Path Forward

The project has outlined specific milestones for the coming year:

For Q1 2025:

• $1M Fundraise

• Initiation of scaled manufacturing runs for ARTAN-102

For Q2-Q3 2025:

• Commencement of animal studies in disease-relevant models

• Presentation of findings at scientific conferences

Pioneer in DeSci Funding

VitaRNA/Artan Bio's journey exemplifies the potential of decentralized science funding. The project began with a $91,000 investment from VitaDAO, registered on-chain as an IP-NFT, followed by a successful $300,000 raise through IP tokenization. This innovative funding model has enabled community members to directly participate in advancing potential longevity therapeutics.

Team and Support

Led by top biotech experts with a proven track record in advancing drug development to clinical trials, CEO Anthony Schwartz (@aschwartzphd) and CSO Michael Torres (@Mykalt45) bring deep industry expertise to the project.

Support the VitaRNA Fundraise here: https://mint.molecule.to/ipnft/28/crowdsale/30703810525592972065907045517072277760884022578353069648383135471698350924972

Join our journey:

• Website: https://vitarna.xyz

• Community: t.me/vitarna

• VitaRNA on CoinGecko: https://coingecko.com/en/coins/vitarna

Help us spread the word: https://x.com/vita_dao/status/1877712287303172499

Introduction

Hello Vitalians and welcome back!

The holidays are fast approaching and with that another exciting year for longevity research is coming to an end. A lot has happened, but in this issue we wanted to bring your attention to something you might have missed. No, not another epigenetic reprogramming therapy or a new senolytic, but something quite different…

We want to introduce you to an innovative approach in longevity research: targeting nonsense mutations and stop codons as a strategy to combat aging.

Nonsense mutations, which create premature stop codons, are responsible for approximately 10-20% of inherited diseases and play a significant role in tumor suppressor gene inactivation in cancer. Recent advancements in biotechnology have opened up new possibilities for addressing these mutations, potentially impacting age-related diseases and longevity.

Researchers are developing novel methods to promote read-through of premature stop codons, restoring the production of functional proteins. This approach holds promise for treating various genetic disorders and could have broader implications for aging processes.

VitaDAO, a decentralized science initiative, is at the forefront of this field through its support of ARTAN Bio. Led by Dr. Michael Torres, ARTAN Bio is developing innovative strategies to address nonsense mutations in rare and age-related diseases.

To gain deeper insights into this cutting-edge research and its potential impact on longevity, we encourage you to read our exclusive interview with Dr. Torres at the end of this newsletter. His journey from cancer biology to longevity research and his vision for ARTAN Bio's future offer a fascinating glimpse into the evolving landscape of biotechnology and aging research.

In other Vita news, our in-house Venture Studio - VitaLabs - is picking up steam with more and more novel ideas brewing. In case you missed it, check out the VitaLabs Forum on Discord and contribute to the discussions. The deadline to apply as a fellow and submit your idea for funding in the $200k quadrating funding round is less than 2 weeks away, so if you’re a late-comer there is no time to waste!

Longevity Literature Hot Picks

Pre-Print Corner

RNA editing is a molecular clock in unmodified human cells

Transcriptome Timestamping (T2) is a new technique that leverages natural RNA editing processes in human cells to determine the age of individual RNA transcripts, providing insights into when genes were active. This method reveals detailed temporal dynamics in gene expression, such as during the transition of monocytes to macrophages, and can be used in single cells to uncover transcriptional changes in diverse cell populations without genetic modification.

Published Research Papers

Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems

A large-scale proteomics study reveals organ-specific aging patterns, linking accelerated aging to chronic diseases and environmental factors. The findings suggest men age faster than women in most organs and advocate for both universal and personalized anti-aging interventions.

Convergent evolution associated with the loss of developmental diapause may promote extended lifespan in bees

Shifts in the diapause stage precede social evolution in Hymenoptera. Comparative analysis of 27 bee genomes reveals potential mechanisms for lifespan extension in species lacking prepupal diapause, including loss of growth hormones and convergent selection in lifespan-regulating genes.

The deacetylase SIRT6 reduces amyloid pathology and supports cognition in mice by reducing the stability of APP in neurons

Research has shown that the enzyme SIRT6, which decreases in activity as it ages, regulates the amyloid precursor protein (APP) implicated in Alzheimer's disease (AD) by promoting its degradation. Enhancing SIRT6 activity pharmacologically in AD mouse models reduced amyloid buildup and improved cognitive functions, suggesting that SIRT6 activation could be a promising therapeutic strategy for combating AD-related symptoms.

Piwi mutant germ cells transmit a form of heritable stress that promotes longevity

In the study of the C. elegans Argonaute protein PRG-1/Piwi, researchers found that late-generation mutants with reduced fertility exhibited increased lifespan, a phenomenon linked to a hormetic stress response mediated by the transcription factor DAF-16. These findings suggest that the inherited stress from prg-1 mutant germ cells, which affects longevity and fertility, could have broader implications for understanding the epigenetic inheritance of lifespan traits in other organisms.

Boosting NAD+ in patients with COPD reduces airway inflammation

A recent study indicates that increasing nicotinamide adenine dinucleotide (NAD+) levels in patients with chronic obstructive pulmonary disease (COPD) for six weeks can decrease airway inflammation and potentially slow biological aging, possibly by reducing cellular senescence. This finding supports the theory that the loss of NAD+ contributes to the development and progression of COPD.

Published Literature Reviews, Hypothesis, Perspectives and more

Gut microbiome and Alzheimer’s disease: What we know and what remains to be explored

Recent studies in human microbiome research have linked gut microbiota dysbiosis—characterized by changes in diversity and the rise of harmful bacteria—to the development of Alzheimer's disease (AD) through the gut-brain axis. This review explores the molecular mechanisms of this interaction and discusses therapeutic approaches such as probiotics, diets, and fecal microbiota transplantation that target gut microbiota to potentially mitigate AD.

Cellular senescence in Alzheimer’s disease: from physiology to pathology

Alzheimer's disease (AD), a prevalent neurodegenerative disorder marked by Aβ accumulation and tau hyperphosphorylation, has prompted research into cellular senescence as a contributing factor to its progression. This review highlights the role of senescence in various brain cells and discusses therapeutic strategies targeting senescent cells, such as using senolytics and senomorphics, as promising approaches for improving cognitive function and reducing AD pathologies.

The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience – Through the lens of the “900-day rule”

Research on lifespan extension often faces challenges due to short lifespans in control groups skewing results, making the efficacy of longevity interventions seem more significant than it may be due to statistical anomalies or other factors. The study suggests using a new "900-day rule" for evaluating mouse longevity studies, recommending high confidence in interventions only when control lifespans are near 900 days or treated lifespans significantly exceed this benchmark, aiming to provide a more reliable method for identifying promising longevity interventions.

Metformin and monkeys: what can we learn about delaying aging?

A recent study has shown that metformin, commonly used to treat diabetes, significantly enhances health parameters in older male cynomolgus monkeys, suggesting it may slow aging. This research marks a significant advance in exploring how drugs could potentially prolong healthspan and delay aging-related diseases in humans.

Job Board

João Pedro de Magalhães is looking for a PhD student to develop and apply computational methods to study ageing and cellular rejuvenation

Jürg Bähler is looking for a Postdoc in Functional Genomics who will apply large-scale genetic assays, functional profiling, and systemic/computational approaches to examine the roles of conserved yet unstudied proteins, with a focus on cellular quiescence and ageing.

Alexandra Stolzing is seeking a Research Associate in Predictors of Resilience and Frailty at the Loughborough University.

Param Priya Singh at UCSF is looking for a postdoc with a background in machine learning and genomics to study the determinants of aging.

News and Media

New Crowdfunding Project Looks for a “Better Rapamycin”

Physical fitness can lower risk of dementia, research finds

Shingles and brain health: an emerging link or healthy user bias?

What’s the secret to living to 100? Centenarian stem cells could offer clues

Weizmann researchers discover why the wee hours of the day can be especially dangerous to our health

Funding

In their 2025 call the BSRA have increased the value of their Summer Studentships and Small Research Grants from £2,000 to £3,000 to reflect increases in costs of living and consumable costs in the United Kingdom.

Prizes

Last month for you to enter the XPRIZE Healthspan!

Conferences

Global Conference on Gerophysics

5th February 2025

Singapore, NUS

Aging: New Frontiers in Rejuvenation and Gerotherapeutics

February 17-20, 2025

Next year, the 89th CSHL Symposium on Quantitative Biology is dedicated to "Senescence & Aging"! Make sure you register (May 28 - June 1, 2025)

Save the date! Marco Demaria announced that the next ICSA meeting will be held in Rome, marking the 10th anniversary of the ICSA meetings.

16th-19th September 2025, Rome, Italy

Tweets of the Month

The Alliance for Longevity Initiatives (A4LI) - What is a biomarker of aging?

Podcasts and Webinars

Biomarkers of Aging | AgingDoc David Barzilai MD PhD @ MIT Media Lab

The Optispan Podcast with Matt Kaeberlein: I Took 4 Different Biological Age Tests & Compared the Results...

Interview with Dr Michael Torres

Bio: Dr. Michael Torres is a biotech entrepreneur, CEO of CrossBridge Bio, and founder and CSO of ARTAN Bio - a VitaDAO spin-out built on the VITARNA IPT. With a Ph.D. from UT Southwestern and experience as VP of R&D at ReCode Therapeutics, he is also an active participant in decentralized science through his work with VitaDAO, advocating for transparent and collaborative therapeutic development.

What inspired you to enter longevity research, given you’ve spent most of your career in cancer biology?

My entry into longevity research stemmed from the multi-disciplinary training I received at UT-Southwestern, where I completed my Ph.D. In most respects, cancer stems from the dysregulation of cellular processes that are associated with aging. As I completed my Ph.D. training, I became interested in developing therapies to correct nonsense mutations that cause cystic fibrosis and pre-mature aging diseases such as Werner’s syndrome. It was this biology that I realized could have broader impacts on aging. With the support of VitaDAO, we’ve developed a therapeutic that could have wide implications against aging.

What mistakes do you think the longevity field has made?

The longevity field has faced challenges such as overhyping preliminary findings and underestimating the complexity of aging. The field has often embraced public figures who promote interventions that don’t have solid scientific backing. These missteps have led to public skepticism and hindered progress. That said, there continue to be great strides in understanding the aging process and how we could slow or reverse aging. Additionally, there continues to be more and more investment in the space to allow biotech to develop and test interventions properly, such as randomized, placebo-controlled clinical trials.

What do you think have been the biggest or most important discoveries in the aging field?

I’m a big believer in the power of human genetics as a guide to understanding how genes and cellular pathways could be targetable for a given disease. As we identify more humans with mutations that predispose or protect against aging, this has led to more hypothesis generation and the development of interventions that impact these pathways. I believe these efforts will bear fruit.

What advice would you give to people currently working in longevity research?

My advice would be to follow the science and be critical of your own work and the work of others. Additionally, think carefully about your experiments and always have the proper controls!

How has the biotechnology landscape changed since you began your career, particularly in areas like ADCs and rare disease therapeutics?

Since the start of my career, the biotechnology landscape has evolved remarkably, particularly in developing antibody-drug conjugates (ADCs) and therapies for rare diseases. Advancements in linker technologies and payload diversification have enhanced ADC efficacy and safety. Additionally, the rise of genetic medicine has transformed the treatment paradigm for rare diseases, offering hope to previously underserved patient populations.

What do you think are the most pressing unmet needs in the current biotech ecosystem?

There are many people out there with good ideas. The challenge remains on how best to fund them. Academic grants are great for fundamental science but are not optimized for translating these ideas. Venture capital (VC) is typically risk-averse, so funding early-stage derisking is only possible with solid connections to VC and pharma. Therefore, seeing how DeSci and tokenized IP are stepping in is exhilarating.

What drew you to the decentralized science space, and how do you see its role evolving in biotechnology and therapeutic development?

Funny enough, my entry into the DeSci space came from a friend at Pfizer Ventures. Pfizer is one of the most traditional pharmaceutical companies out there. I was unfamiliar with the DeSci space at the time but was asked to engage with VitaDAO as they were evaluating interesting science and wanted to do spinouts as well. The community welcomed my background as a scientist, successful entrepreneur, and drug developer. I see the opportunity of DeSci as the following: DeSci can facilitate more transparent, collaborative, and efficient therapeutic development, potentially accelerating the translation of scientific discoveries into clinical applications.

ARTAN Bio’s approach to addressing nonsense mutations is novel. Could you explain how your technology differs from existing methods and why it holds promise for rare and age-related diseases?

ArtanBio's approach to addressing nonsense mutations involves innovative strategies to promote the read-through of premature stop codons, thereby restoring the production of functional proteins. This method differs from existing therapies by specifically targeting the translational machinery to overcome these mutations. Another exciting aspect of our approach is that we target a specific type of nonsense mutation found in many genes that code for proteins involved in many cellular processes involved in aging, such as DNA repair and tumor suppressors. If the science plays out, our one intervention could address multiple aspects of aging.

Where do you see ARTAN Bio in the next five years, and what impact do you hope it will have on the field?

We’re excited for what’s in store for Artan Bio. We’ve been transparently working hard to prove that DeSci has real potential to find and develop assets that have real-world value. We want to be the poster child for what DeSci can do. We must continue doing rigorous experiments that move our assets further through the drug development pipeline. We hope to start IND-enabling studies in 2025, be in the clinic in 2026 with our first asset, Artan-102, and work toward FDA approval within 5 years. If we’re successful, this would prove that DeSci is more than a movement; it’s an engine to foster the development of novel therapeutics. How’s that for impact!

Outro

We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful in helping you to keep up-to-date with all the exciting longevity-related developments. See you next month!

Further Reading

Molecular and Cellular Effects of Microplastics and Nanoplastics: Focus on Inflammation and Senescence

Photobiomodulation ameliorates ovarian aging by alleviating oxidative stress and inflammation damage and improving mitochondrial function

Convergent evolution of senescent fibroblasts in fibrosis and cancer with aging

Causal inference for epigenetic ageing

During the latest VitaDAO community call, the VitaFast team shared an exciting breakthrough in their autophagy research. Their initial lead compounds had already demonstrated a statistically significant improvement of 2-3 times greater autophagy induction compared to rapamycin.

Now, VitaFast’s newest compounds have shown even more promising results, exhibiting 10-100 times higher potency than their previous lead series! This increase in potency provides the team with considerable flexibility in optimizing dosage protocols to balance safety and maximize autophagy activation.

While these results need extensive further testing, they mark an important milestone in the project's mission to enhance autophagy - the natural process cells use to remove damaged components, which slows down as we age.

Project Lead Oliver, working with researchers at the University of Newcastle, presented their work on developing these compounds that could trigger cellular cleanup more effectively than current methods like fasting. Think of autophagy like your cell's recycling system: when it works well, your cells stay healthy longer.

These lab results are particularly interesting because rapamycin is considered a benchmark in aging research. However, it's important to note that these results are from early cell studies - the next crucial step is testing whether this improved performance holds up in living organisms.

What they've done so far:

• Found new compounds through careful screening and testing

• Developed lab tests to make sure the compounds work as intended

• Focused on making sure cells can complete the entire cleanup process

• Designed brand new, wholly owned, compounds to target the process

• Successfully showed their compounds can activate cellular cleanup in lab tests

What's coming next:

• Start testing compounds in worms (a common first step in aging research)

• Protect discoveries through patents

• Run more experiments to understand exactly how well these compounds work

• Test the compounds in different types of cells and organisms

The team is taking a careful, step-by-step approach to validate their findings. This matters because if successful, their work could lead to new ways to support healthy aging.

For VitaDAO members interested in the technical details: the team uses multiple testing methods including P62 clearance and LC3 assays, with special attention to lysosomal fusion in the autophagy process.

Watch the full update:https://x.com/i/broadcasts/1jMKgBODrNAxL (min 36+)

Learn more:

https://vitafast.xyz

Join the community: https://t.me/fastvita

Coingecko:https://www.coingecko.com/en/coins/molecules-of-korolchuk-ip-nft

Introduction

Welcome back Vitalians!

Last month we announced the launch of our new Venture Studio - VitaLabs - now we would like to give you more information on how you can get involved!!

In order to attract top talent into VitaLabs, we are running a Fellowship program looking for creative and independent thinkers passionate about longevity to collaborate, ideate, and develop groundbreaking ideas.

October 2024 Longevity Research Newsletter

Introduction

Welcome back Vitalians!

Last month we announced the launch of our new Venture Studio - VitaLabs - now we would like to give you more information on how you can get involved!!

In order to attract top talent into VitaLabs, we are running a Fellowship program looking for creative and independent thinkers passionate about longevity to collaborate, ideate, and develop groundbreaking ideas.

We're looking for ideas that could result in longevity therapeutics or diagnostics, but are perhaps too early, risky or “out-of-the-box” for traditional funding. The bolder and more disruptive the better!

We are currently in the Ideation Stage of our roadmap!

Prospective Fellows are required to ideate with the community and submit a project proposal by 30th December 2024, with up to 4 projects receiving a split of $200k from VitaDAO.

VitaLabs will then commission CROs to conduct experiments, with promising projects then going on to be minted as an IP-NFT and tokenised (IPT) to raise further funding, and potentially spun out into new start-ups. 

Project leads (2 per project max) of funded projects will become VitaLabs Fellows, receiving: mentorship and support, a minimum of 10% of IPTs, a $2k/month stipend for 4 months and a performance bonus in VITA tokens.

However, you don't need to be a project lead to get involved and get rewards - we will also be offering IPTs for community members who make creative/intellectual contributions to funded projects, no matter how small!

What do I need to know? 

Whether or not you have an idea, please apply to the VitaLabs Fellowship Program. Then come and join the VitaLabs channel in VitaDAO’s Discord and introduce yourself!

If you have an idea, great, come and discuss your idea with the VitaDAO community on the channel. We’ll all help you to strengthen your idea and formulate a plan to put a solid funding proposal together.

If you don't have an idea, don’t worry, come and join the discussions for any projects that interest you and be rewarded with a share of the IPT for any contribution, no matter how small!

Full information about the timeline and roadmap of the program can be found here. We look forward to welcoming you into the VitaLabs community!

____

In other news, a recent paper published by Prof. S. Jay Olshansky - Implausibility of radical life extension in humans in the twenty-first century - has been causing quite the stir among the scientific community. You can read the accompanying news and views here. At VitaDAO we love to support disruptive ideas and are incredibly excited to bring you an interview with Prof. S. Olshansky at the end of this newsletter. Enjoy!!

Longevity Literature Hot Picks

Published Research Papers

Implausibility of radical life extension in humans in the twenty-first century
The paper examines trends in life expectancy from 1990 to 2019 in the world's longest-lived populations, revealing a deceleration in mortality improvements and suggesting that radical life extension is unlikely without significant breakthroughs in slowing biological aging.
But don’t take our word for it - check out our full interview with Jay Olshansky himself down below!

Metformin decelerates aging clock in male monkeys

A 40-month study on male cynomolgus monkeys revealed that metformin significantly delays aging, including a remarkable reversal of brain aging by about six years, while preserving brain structure and cognitive function. Using advanced biological analyses, the study demonstrated metformin's potential to reduce overall biological age in primates, highlighting its promise for developing anti-aging therapies in humans.

Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity

At the 2023 Aging Research and Drug Discovery Meeting, experts highlighted the role of AI, biomarkers, geroscience, and biotechnology in combating age-related diseases and extending healthspan through innovative interventions and technologies. Huge collaborative effort!

Identifying specific functional roles for senescence across cell types

This study developed a genetic toolkit to trace, ablate, and manipulate p16Ink4a+ senescent cells, uncovering their distinct roles in liver fibrosis and repair. It revealed that clearing p16Ink4a+ macrophages reduces liver damage, while removing p16Ink4a+ endothelial cells worsens injury, highlighting the need for cell-type-specific senolytic therapies to address aging and disease.

Dietary restriction impacts health and lifespan of genetically diverse mice

This study evaluated the effects of caloric restriction and intermittent fasting on the health and lifespan of genetically diverse female mice, finding that both approaches extended lifespan in proportion to the level of restriction. However, health effects varied, with 40% caloric restriction showing the strongest lifespan benefits but causing lean mass loss and immune changes, while intermittent fasting had limited effects in certain mice, underscoring the complexity of aging interventions and the need to define appropriate health and lifespan metrics.

A hematology-based clock derived from the Study of Longitudinal Aging in Mice to estimate biological age

This study developed a blood-based aging clock using routinely collected hematological markers and a deep neural network to predict biological age and assess the "aging gap" between biological and chronological age in mice. The aging gap was linked to frailty and mortality risk, with platelets emerging as the strongest age predictor, highlighting the potential of this approach as a practical tool for studying aging variability.

Is castration leading to biological aging in dogs? Assessment of lipid peroxidation, inflammation, telomere length, mitochondrial DNA copy number, and expression of telomerase and age-related genes

This study investigated the effects of castration on biological aging in male dogs, finding that castrated dogs exhibited reduced lipid peroxidation and inflammation, along with preserved telomere length and mitochondrial DNA copy number. Gene expression analysis also indicated delayed age-related changes, suggesting that castration may have a protective effect against biological aging in dogs.

Human iPSCs from Aged Donors Retain Their Mitochondrial Aging Signature

Aging is a major risk factor for neurodegenerative diseases, partly due to mitochondrial dysfunction, a key hallmark of aging. This study reveals that induced pluripotent stem cells (iPSCs) from aged donors show impaired mitochondrial function, offering a potential model to screen drugs that target mitochondrial aging and promote healthy aging.

Published Literature Reviews, Hypothesis, Perspectives and more

Selective autophagy: a therapeutic target for healthy aging?

Aging at the molecular level involves the accumulation of cellular damage to DNA, proteins, and organelles, which autophagy—a cellular recycling process—helps mitigate by degrading and recycling damaged components. This review explores the roles of macroautophagy, microautophagy, and chaperone-mediated autophagy in maintaining cellular health, their contributions to aging, and how enhancing these pathways could offer therapeutic strategies for healthy aging.

The brain–body energy conservation model of aging

Aging involves increased cellular energy expenditure due to damage-induced stress responses, while overall body energy expenditure remains stable or decreases, a paradox explained by the brain’s role in energy conservation. The brain–body energy conservation (BEC) model suggests the brain responds to energy demands from damaged cells by suppressing low-priority functions, driving aging symptoms like fatigue and immune changes, and shaping how aging trajectories can be modified by interventions.

The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience

Immunosenescence refers to the decline in immune system function with age, affecting both innate and adaptive immunity, leading to increased infection risk, reduced vaccine efficacy, chronic inflammation, and age-related diseases. This review explores the factors influencing immune aging, including sex, age, social determinants, and gut microbiota, while highlighting strategies to enhance immune resilience through lifestyle changes, stress management, and therapeutic interventions to support robust immunity in older adults.

Immunosenescence: A new direction in anti-aging research

Immune aging, the gradual decline in immune system function with age, leads to dysregulated immune cell responses, such as impaired neutrophil chemotaxis and reduced macrophage phagocytosis, resulting in poor vaccination responses, increased inflammation, and autoimmune disorders. This review highlights the cumulative effects of immune aging, including thymic atrophy, reduced hematopoiesis, and chronic inflammation, which elevate the risk of age-related diseases like Alzheimer’s and osteoporosis, suggesting that targeting immune system changes could be a promising anti-aging strategy.

Contextualizing aging clocks and properly describing biological age

The term "biological age" is often used interchangeably with the outputs of aging clocks, but it is a broader concept reflecting an individual's internal, external, and functional aging. Since aging is tissue-specific and highly complex, the authors recommend labeling aging clock outputs based on their input data (e.g., epigenetic age or transcriptomic age) or the clock's name to avoid conflating specific biomarkers with the multifaceted concept of whole-body biological age.

The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression

Senescence and epigenetic alterations stand out as two well-characterized hallmarks of aging. When cells become senescent, they cease proliferation and release inflammatory molecules collectively termed the Senescence-Associated Secretory Phenotype (SASP). Senescence and SASP are implicated in numerous age-related diseases. Senescent cell nuclei undergo epigenetic reprogramming, which intricately regulates SASP expression. This review outlines the current understanding of how senescent cells undergo epigenetic changes and how these alterations govern SASP expression.

News and Media

Eli Lilly considers testing weight-loss drugs on people who are not overweight

“Blue Zones” are coming under the microscope:

Blue Zones: A Review of the Netflix Documentary

Do People in ‘Blue Zones’ Actually Live Longer?

Mayo Clinic study: What standing on one leg can tell you

Research in Context: Can we slow aging?

‘Do you really want to live forever?’ Sci-fi author Ted Chiang talks immortality

A Senolytic Treatment for Liver Sepsis

I've studied longevity for nearly 25 years: Here's what I prioritize to have a long, happy life

Unlocking Longevity: How Rapamycin Could Be the Key to Extending Healthspan

Eating less can lead to a longer life: massive study in mice shows why

Scientists Have Discovered a Dietary Compound That Increases Longevity

Resources

We’d like to share 2 great resources from Karl Pfleger this month. One, a list of aging biotech companies, and two, an essay by Karl on the classic longevity question “Is ageing a disease?”

Prizes

There are just 3 months left to enter XPRIZE Healthspan!

Job Board

An exciting PhD project in Graeme Hewitt’s lab (King’s College London) in collaboration with Professor Elinor Sawyer. Bystander-Balance: Modulating cell death in bystander cells to improve therapy response. Potential to start in Feb so check it out here

Yale Center for Research on Aging (Y-Age) are seeking applications for up to 2 tenure-track positions at Asst. or Associate Professor level to build an interdisciplinary research program in basic biology of aging. They are seeking outstanding scientists interested in aging & geroscience. Apply here

Alexei Maklakov has a PhD position available in the evolution of ageing at the University of East Anglia: Testing the evolutionary theory of ageing: from genes to populations. Apply here

Conferences

Aging: New Frontiers in Rejuvenation and Gerotherapeutics

February 17-20, 2025

Next year, the 89th CSHL Symposium on Quantitative Biology is dedicated to "Senescence & Aging"! Make sure you register (May 28 - June 1, 2025)

Podcasts and Webinars

Geroscience - Extending Healthy Lifespan: A Healthspan Primer for Friends and Family

Your ‘Biological Age’ Could Be Different Than How Old You Are

Interview with S. Jay Olshansky, PhD

S. Jay Olshansky received his Ph.D. in Sociology at the University of Chicago in 1984. He is currently a Professor in the School of Public Health at the University of Illinois at Chicago, Research Associate at the Center on Aging at the University of Chicago and at the London School of Hygiene and Tropical Medicine, and Chief Scientist at Lapetus Solutions, Inc. The focus of his research to date has been on estimates of the upper limits to human longevity, exploring the health and public policy implications associated with individual and population aging, forecasts of the size, survival, and age structure of the population, pursuit of the scientific means to slow aging in people (The Longevity Dividend), and global implications of the re-emergence of infectious and parasitic diseases.

What inspired you to enter longevity research?
I was in graduate school at the University of Chicago in the late 1970s with an interest in adolescent fertility, but my advisor suggested I take a course in human development from Bernice Neugarten. During that class, Bernice was discussing her now famous phrase distinguishing between health and age – “young-old and old-old” – and I commented that I thought all older people were the same. Bernice of course knew otherwise as I was a young inexperienced graduate student, but instead of correcting me, she gave me an assignment to write a paper on what the demographic consequences would be if science were to successfully slow aging in people. This was the topic of a recent book she published on the topic, which she handed to me at the time. I entered the Regenstein library that semester, and it felt like I didn’t leave for two years – I was enthralled with the question about how long humans can live. Bernice encouraged me to turn the resulting paper into my master’s thesis, which I did, and she later became part of my dissertation committee on a related topic about human longevity.

Which of the current theories of ageing do you think are the most convincing?
The answer depends on which theories you’re referring to – the “why” question or the “how” question. My first instinct is to think of evolutionary theories of senescence because evolution is always at the top of my thinking about ageing and longevity. If that’s what you mean, I favor all three major theories developed by Sir Peter Medawar, George Williams, and Tom Kirkwood; indeed, all three may be correct. If you mean the “how” question, I hold no favorite.

How has the field changed since you started?
When I first started working in the field of ageing in the late 1970s, the field of gerontology itself was still nascent. The founding director of the National Institute on Ageing – Dr. Robert Butler (Uncle Bob as my wife and I used to refer to him) brought me under his wing. Bob spent an enormous amount of time educating the public on the importance and value of gerontology, and he appreciated my angle on the world of ageing because it combined the demographic and biological sciences into the new field of Biodemography that my colleagues and I helped to launch in the 1990s. Bob invited me to speak at most if not all of the Age Boom Academy meetings he held in New York through the International Longevity Center he created. I still recall a scientific meeting that Bob convened in Arizona decades ago where we (scientists from various disciplines) spent time trying to think of an alternative phrase to ‘anti-ageing medicine’ to describe the valuable work that was going on in the various fields of ageing (none of us were against growing older, it’s the consequences of ageing we were after). I believe we settled at the time on “Ageing Science”, but this eventually morphed into “The Longevity Dividend”, and then “Geroscience”. 

There are several important developments that have happened in the last four decades. The theoretical underpinnings of Geroscience have come together to answer the “why” question about ageing. Gerontology itself has come of age as the world has rapidly grown older; the baby boom generation is driving much of the demand for advancements in the science of ageing since this generation has reached the age where senescence has become noticeable; advances along multiple fronts in efforts to understand and modulate ageing across multiple species have been dramatic; funding for Geroscience has accelerated dramatically; the FDA now fully understands the value of having a single intervention influence multiple disease endpoints; entire new departments at Universities across the globe now support Geroscience; Biodemography and The Longevity Dividend/Geroscience are now the subject of both conferences and labels for entire University departments; funding for Geroscience has skyrocketed for a multitude of reasons; and large companies and billionaires have jumped in for profit or fame or both. The National Geographic special entitled The Age of Aging that came out in 2016 proved to be an important catalyst for the field. I could go on because the list is long but suffice it to say that the field has changed dramatically in the last few decades – mostly for the good in recent years.

What mistakes do you think the longevity field has made?
The longevity field dates back thousands of years, and therein lie the earliest mistakes; many of which are still being made today – exaggeration, embellishment, dangerous experiments, emergence of the wild west of aging interventions, and the 10-year curse. I addressed these issues years ago in an essay entitled “Don’t Fall for the Cult of Immortality” and a book chapter entitled “Why Do Anti-Aging Doctors Die?”, so I won’t repeat those arguments here. For now, I’ll focus on the present.

Here are some of the mistakes in a nutshell.
Embellishment/exaggeration: There is a tendency among some in the field to claim that one intervention or another will allow humans to live to a specified age; 100, 150, 200, 500, 1000, immortality – I’ve seen all of these numbers used. They’re all made up out of thin air – there is no scientific basis for choosing any of them, especially not by extrapolating from other species to humans where life is lived on different time scales, and there can be no empirical evidence that whatever is being sold can make humans live to any of these ages. Since claims of radical life extension are untestable scientific hypotheses because of the time it takes to verify the claim, there is no point in making them up. I’m a bit surprised that investors are buying into these claims since they should already know that those making them cannot demonstrate success.

Dangerous experiments and the wild west of ageing interventions: As I read contemporary claims of radical life extension without evidence to back it up, I’m reminded of the excitement about similar claims being made for using growth hormone as an elixir of youth in the 1980s – until it was later discovered to be linked to cancer. This ruse even went so far as to have physicians prescribing GH under off-label use as an anti-ageing therapeutic, which was later shown to be illegal – not to mention dangerous. I attended a conference in early 2024 in Roatan where an effort is underway to create an environment where experiments in ageing science can be accelerated outside of the purview of the FDA or its equivalent safeguards – by allowing people to come there and experiment on their own bodies with the latest ageing therapies. At one level the folks creating this accelerated “research” environment are taking matters into their own hands because they recognize the importance of getting a gerotherapeutic into the hands of a rapidly ageing world – including especially those funding these experiments. If their experiments actually work, they will have contributed to one of the most important public health advances in medical history and would indeed be held up as heroes in the medical and ageing worlds. I have great admiration for this goal as I hold the same ideals, but not at the expense of potentially risky experiments and naïve billionaires or millionaires willing to experiment on themselves or others. If anyone dies during these experiments in Roatan or elsewhere, even if unrelated to the ongoing interventions, it will likely bring a lot of good work in the field to a grinding halt.  

The 10-year curse: Go back in time to the Prolongevists of the past 2,000 years, and you’ll find a common theme – all described in the first chapter of my book The Quest for Immortality. When asked when their potion or elixir will generate everlasting life, or at the least radical life extension, the answer given is almost always 10 years. Even the alchemists from centuries ago fell prey to the 10-year curse as they needed to justify to their investors that the effort to transmute lead into gold would occur in enough time for the investor to benefit from the advance. I vividly recall a well-known researcher in the field of ageing sitting across from me during an interview with the BBC in the year 2000. When asked when the “breakthrough” would happen, this researcher naturally fell prey to the curse. I smiled when I heard this answer, only to later give the answer to this question that I think is most appropriate – which is that I hope a gerotherapeutic comes online and is shown to be safe and efficacious in enough time to benefit most people alive today.

Other than your own, what do you think have been the biggest/important discoveries in the field?
My own research does not qualify as one of the most important discoveries in the field. My first instinct is to once again pivot to the field of evolution biology because it was the answer to the “why” question that drives all of our understanding of the timing of death and the expected duration of life of species. In my view (influenced by Theodosius Dobzhansky’s famous quote), “nothing in biology makes sense except in the light of evolution” – so I would count the evolutionary theories of senescence as foundational. Then I move to the central question I’ve been addressing, which is how long humans can live at the individual and population level. Here the answer is easy – Benjamin Gompertz and his discovery of the “law of mortality” in his 1825 article. Many researchers in the field may be unaware of Gompertz, but our current understanding of why humans and other species live as long as we do, and how much longer we might live, has its intellectual and mathematical origins with Gompertz. When Gompertz’s “law of mortality” was explained by the evolutionary theories of senescence, it became immediately obvious how long humans can live and why. All of the advances in public health and medicine and aging science in the last two hundred years, are fundamentally influenced by these discoveries. Public health had the greatest impact on allowing ageing to become commonplace as it allowed most people to experience this phenomenon – ageing is rarely seen in most animals in the wild. Later in the 20th century advances in medicine led to the manufacture of survival time beyond what I refer to as the natural limit to human longevity – which has been estimated to be in the 30-60-year range – the first “soft” limit. Since most people alive today past age 60 are living on ‘manufactured time’ that was granted to us by medicine, long-lived populations are essentially patched together quite effectively by technological advances that did not exist for most of humanity’s existence. Humanity broke through the first ‘soft limit’ to longevity in the early 20th century when life expectancy at birth exceeded 60 years – I believe we’re now approaching the second soft limit as life expectancy approaches 85-87 years. The life expectancy limitations I speak of in the latest paper represent the diminishing longevity returns that follow naturally from the competing risk environment the world has entered.

I realize you might have been expecting an answer that veered into aging biology, but it’s too early to tell which of the many developments in the field will become the most important discoveries. However, if pressed to give an answer, it would be the discovery that ageing itself is inherently modifiable – it is a legitimate target that is ripe for intervention. If the avoidance of ill health is the metric of success representing the value of a discovery, there is no doubt that public health’s success in reducing early age mortality enabled most people to live long enough to experience ageing. These developments added a massive number of person-years of life more than a century ago, but this advance influenced only a relatively small segment of the population. By contrast, a successful gerotherapeutic will prove to be far more important (and valuable) as a medical breakthrough because of its ability to manufacture healthy life for a much larger segment of the population (nearly everyone in developed nations) relative to gains produced by public health.  

What advice would you give to people currently working in longevity research?
Longevity research, or ageing science as I prefer, has emerged as potentially one of the most important new developments in public health to come along since the introduction of vaccines and antibiotics. Scientists and public health advocates and funders for this groundbreaking work, are now in the process of funding, developing, testing for safety and efficacy, and eventually manufacturing what I consider to be the most precious commodity on earth – healthy life. To the investors, your contribution to the advancement of science and medicine is foundational and at least on par with the great public health innovators of the 19th and 20th centuries. To the scientists, you’ve embarked on a public health journey of great importance, but this journey comes with a heavy responsibility to ensure safety first, then efficacy. When the science is done right and these pillars of public health are upheld, a viable gerotherapeutic will carry the designation of one of the most important public interventions in the modern era. The value of such an intervention to the individuals whose lives will be changed cannot easily be calculated in monetary terms since it’s difficult to put a price on a healthy year of life, but for national economies the value of a gerotherapeutic has been estimated to be $38T for just one year of healthy life. There is reason to believe the value to national economies of a successful gerotherapeutic could be much greater. In short, for those investing in and working on ageing science, we are on the cusp of a breakthrough that will change the face of human ageing for most current and all future generations.

In light of your recent paper “Implausibility of radical life extension in humans in the twenty-first century” how do you see current public perceptions around "radical life extension" diverging from the scientific reality?
As I was doing interviews with the media following the publication of our Nature article, one common theme that emerged was that the reporters almost universally believed the narrative that all of humanity has been promised a lifespan of 100 years. At least that’s what they came to believe from some scientists in the past three decades, so they were more than a bit surprised at our conclusions. Once I explained that life expectancy at birth must decelerate as long as the biological process of ageing is immutable – and now we have three papers published during the last 34 years documenting the fact that the deceleration has already occurred – they understood the message. The reporters came into the interview expecting a dour assessment of the human condition, but our argument is that the slowdown in the rise in life expectancy is a product of success – not failure. Ours is a positive message – not a negative one. When enough people in a given cohort become exposed to the currently immutable force of the ageing of their bodies, the patchwork of manufactured time that modern medicine has given humanity must yield diminishing longevity benefits. The evidence for this phenomenon is now definitive. My message to the reporters was to find a way to communicate this reality to the outside world – not as a message that humanity is at the end of our longevity rope, but rather, as a celebration of the success of medicine in manufacturing our longer lives and as a clarion call to change our goal from life extension to health extension. We too would like to see humanity live longer; just not at the expense of extending healthy life. Since claims of radical life extension remain untestable scientific hypotheses, in Geroscience we don’t need embellishment and exaggeration to justify the new science of ageing that has the potential to transform what it means to grow older. 

Almost without exception, I’ve seen a gratifying turnaround in public perceptions about ageing and longevity just since the beginning of October. On the one hand I’ve seen realism set in that a life expectancy and lifespan of 100 is not in the cards for most people and countries – contrary to claims made by some mathematical demographers – but this has been accompanied by the excitement attached to contemporary efforts to extend healthspan through anticipated advances in Geroscience. The positive but realistic message we have been conveying in various ways since our original article in Science was published in 1990, has become reality – at least from what we’ve seen just within the past six weeks.

You introduce the concepts of 'second soft limit' to life expectancy and "manufactured time". Can you elaborate on what these entails and how they might influence future longevity research priorities?
Let’s begin with the “first soft limit”, which is defined as how long humans would live in the absence of all medical interventions (no surgeries, dentistry, vaccines, pharmaceuticals, etc. etc.). Under these conditions I believe the life expectancy at birth for humans would be around 60 years – perhaps lower – which would be consistent with the historical record. Humanity broke through that record in the early 20th century by successfully manufacturing more than two decades of life with a life expectancy of about 80 years. It is important to recognize that the natural limit to human longevity is behind us, not ahead of us, as this provides perspective on the concept of “manufactured time”. Most people now alive past age 60 are living on survival time that was created for us by modern medicine. The result has been a rise in the prevalence of ageing related conditions, which realistically should be thought of as a product of success. To be clear, the rise of cancer, cardiovascular diseases, other ageing related causes of death, and a suite of non-fatal disabling conditions, are byproduct of success, not failure. We experience these conditions because we now routinely survive into age windows where these diseases have an opportunity to express themselves. We surmised in our Science article in 1990 that when about 80 percent of a birth cohort survives beyond age 65, the rise in life expectancy at birth should slow to trickle – and perhaps even stop rising altogether once it reaches 85 (82 for men and 88 for women). In our latest paper we provided evidence to suggest these limits could be slightly higher than previously thought (87 for national populations, 84 for men and 90 for women). This should not be thought of as a brick wall for longevity, but rather, a second “soft limit” that emerges as the currently immutable force of biological ageing becomes the dominant risk factor in a population. Humanity is nearing this second soft limit now.

What role do you believe geroscience and the development of gerotherapeutics will play in overcoming these longevity limitations? What do you think are the most promising areas of this research?
This question implies that Geroscience is being developed exclusively to overcome longevity limitations. I see this as the wrong way to look at Geroscience. This question addresses, in part, the earlier question about what mistakes are being made in the field. While I have no problem recognizing that further life extension will result from Geroscience, this should be a secondary goal – the primary goal should be health extension. My view here harkens back to a foundational view that the natural limit to human longevity is actually far behind us – by decades – and that most people alive today at later ages are living on survival time that has already been successfully manufactured by modern medicine. By contrast, protagonists for limitless longevity hold that the life expectancy limit for our species remains ahead of us on the invisible horizon. It is critically important to understand the distinction between moving away from a longevity limit vs moving toward one. The former is like stretching a longevity rubber band, so the further from the natural limit the more difficult it becomes to patch us together to live longer (this is what our research during the last three decades has demonstrated); the latter incorrectly assumes that a natural longevity limit is beyond the horizon and humanity just needs to avoid the harmful behavioral risk factors that are holding us back. Indeed, many of today’s medical and pharmaceutical interventions have successfully overcome the harmful behavioral risk factors that have accumulated in longer-lived populations today. Stents and statins and pharmaceuticals and surgery – among many other medical interventions – successfully combat the obesity, diabetes, cardiovascular diseases, cancer, and many other ailments linked to the ageing of our bodies – at least for those able to avail themselves of these developments.

As for promising areas of research in Geroscience, I’ll leave that to the growing number of scientists in the field that are conducting groundbreaking work on efforts to demonstrate that modulating ageing in humans is possible. My preference is that we pursue all of the options that offer promise – not knowing in advance which one will work. It seems likely that there will be multiple pathways to an ageing intervention – it’s a race to healthspan extension that I’m glad is ongoing.

You famously bet with Steven Austad that no one born before 2000 would live to be 150 years old. Do you still feel confident in your position, or have any recent scientific advances made you reconsider / what would data could make you reconsider?
I’m more confident now than when we made the bet. Since then, there has been absolutely no movement in the tail of the human survival distribution – no one has even come close to the world record 122-year longevity experienced by Jeanne Calment. In fact, there has been imperceptible movement in the number of supercentenarians. Even if a discovery was made today that was documented to be a gerotherapeutic with a systemic influence on multiple disease endpoints, the youngest person to use it would be 25 years old – with a quarter century of accumulated damage to their body. I’m hopeful that a gerotherapeutic will become available before the birth cohort of 2000 reaches 35 years of age, but with each passing day the probability that Steve will win the bet grows dimmer because the available population from which at least one lucky person must emerge and benefit from a theoretical breakthrough in ageing science and live decades beyond the current world longevity record, becomes smaller across time. The only data that would make me reconsider my highly favorable position on this bet is if a gerotherapeutic comes online and those taking it experience either zero mortality for an extended period at older ages, or we see a significant change in the slope of the intrinsic mortality curve past age 65. As such, I’d like to thank Steve in advance for contributing to the future success of my genetic lineage.

Outro

We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful in helping you to keep up-to-date with all the exciting longevity-related developments. See you next month!

Further Reading

Mitochondrial fatty acid oxidation drives senescence

Augmented gut hormone response to feeding in older adults exhibiting low appetite

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Introduction

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Longevity Literature Hot Picks

Pre-print Corner

Systemic extracellular acidification is a hallmark of aging

Published Research Papers

Targeted partial reprogramming of age-associated cell states improves markers of health in mouse models of aging

This study explores a targeted gene therapy approach to slow aging and extend lifespan by delivering specific genes (OSK) to reprogram aged or stressed cells in mice. The therapy improved health markers, delayed aging signs, and extended lifespan without causing tumors, showing potential for future treatments to enhance human health and resilience in aging.

Probabilistic inference of epigenetic age acceleration from cellular dynamics

This research highlights limitations in current epigenetic clocks used to measure biological aging, as they can be influenced by factors unrelated to aging. To improve accuracy, the researchers developed a new model that distinguishes between two key processes, acceleration and bias, which more directly reflect cellular changes and better correlate with factors affecting aging like smoking and alcohol consumption.

Fundamental equations linking methylation dynamics to maximum lifespan in mammals

This study explores how the rate of change in DNA methylation relates to maximum lifespan across various mammal species. The findings show that in specific chromatin regions, there is an inverse relationship between methylation rate and lifespan, with younger animals' methylation patterns reflecting those of older animals, but the overall methylation level doesn't correlate with lifespan.

Rejuvenation of aged oocyte through exposure to young follicular microenvironment

This study shows that the aging of follicular somatic cells, which support oocyte development, may contribute to fertility decline. By transplanting aged oocytes into young follicles, researchers demonstrated improved oocyte maturation, mitochondrial function, and developmental potential, suggesting that future therapies targeting these somatic cells could help treat female infertility.

Hematopoietic aging promotes cancer by fueling IL-1⍺–driven emergency myelopoiesis

This study reveals that aging of the immune system, rather than the age of the tumor itself, promotes lung cancer progression by increasing the production of inflammatory cells that accelerate tumor growth. Targeting the IL-1⍺ signaling pathway, which is linked to age-related immune changes, could help slow cancer development and improve survival in older individuals.

E5 treatment showing improved health-span and lifespan in old Sprague Dawley rats

This study investigates the effects of a plasma-derived treatment (E5) on aging in older rats, showing that E5 improved strength, reduced inflammation and oxidative stress, and enhanced organ health. The treatment significantly extended the rats' lifespan and maintained normal cellular structure, suggesting E5 may be a promising therapy for promoting healthy aging.

A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring

This study analyzed blood samples from centenarians and their offspring to better understand the biology of longevity and resistance to aging-related diseases. By creating high-quality stem cell lines from these samples, researchers developed a unique resource that could help discover new therapies for aging and enhance our understanding of healthy aging and resilience.

Published Literature Reviews, Hypothesis, Perspectives and more

The paradox of senescent-marker positive cancer cells: challenges and opportunities

This study examines the paradox of some cancer cells showing both proliferation and markers of senescence, despite senescence being a natural anti-tumor mechanism. The researchers discuss the challenges in detecting these senescent-marker-positive cancer cells and explore potential strategies to exploit senescence for cancer treatment.

Genetic origins, regulators, and biomarkers of cellular senescence

This review delves into the molecular and genetic factors driving cellular senescence, focusing on stressors like DNA damage, telomere shortening, and oncogene activation. It also explores the intricate signaling pathways involved in senescence, highlighting potential therapeutic targets for aging-related diseases and future research directions for better understanding and treating senescent cells.

News and Media

BioAge brings in almost $200M from IPO as obesity biotech joins Nasdaq

Metformin Slows Aging in Non-Human Primates

Axolotls seem to pause their biological clocks and stop ageing

Boehringer, Insilico Appear to Break Through Against IPF

Scientists find plant-like behavior in human cells

LYCHOS is a human hybrid of a plant-like PIN transporter and a GPCR

Targeting Senescent Cells by Their Surface Markers

Highlighting the nature of epigenetic aging

Job Board

Gabi Desdín is looking for a new PhD student to join me at the Department of Biomedical Sciences, University of Lausanne. Partial reprogramming of hematopoietic stem cells during aging and bone marrow failure syndromes.

Ora Biomedical is hiring research technician, business development manager and software engineer.

Prizes

There are just 3 months left to enter XPRIZE Healthspan!

Conferences

Biomarkers of Aging

November 1-2, 2024, Boston, MA

Aging: New Frontiers in Rejuvenation and Gerotherapeutics

February 17-20, 2025

Tweets of the Month

Alan Tomusiak

Introducing the *longevity spectrum!*

The longevity field is tough in that encompasses anything from supplement companies to body replacement. To make some sense of it, I've arranged the community in a series of "levels" based on hardcore-ness.

Where would you place yourself?

Lada Nuzhna

I will likely be executed for high treason for saying this but I strongly believe that mechanisms for aging prevention and mechanisms for fixing age-related diseases are 2 almost completely different subsets of targets, which is why I think many aging-minded companies will likely fail in the coming decade, with some exceptions*...

Podcasts and Webinars

Mike Mutzel: Choosing YOUR Supplements, Cholesterol & Social Health

Conquer Aging Or Die Trying!

Could This Little Pill Stop You From Aging?

Outro

We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful in helping you to keep up-to-date with all the exciting longevity-related developments. See you next month!

Further Reading

A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank

Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions

A comprehensive map of the aging blood methylome in humans

Reduction in Lp(a) after a medically supervised, prolonged water-only fast followed by a whole-plant-food diet free of added salt, oil, and sugar: a case report

Getting slimmer without dieting or exercising: zebra finches can rapidly lose mass while maintaining food intake and decreasing activity

Accompanying Tweet

Early findings from the NHS Type 2 Diabetes Path to Remission Programme: a prospective evaluation of real-world implementation

Pentadecanoic Acid Supplementation in Young Adults with Overweight and Obesity: A Randomized Controlled Trial

Dissecting the impact of differentiation stage, replicative history, and cell type composition on epigenetic clocks

Analysis of the senescence-associated cell surfaceome reveals potential senotherapeutic targets

NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity

Introduction

Welcome back Vitalians. The VitaDAO team is taking Asia by storm. From Hong Kong to Singapore and Bangkok later in the year! Be sure to catch us there if you’re around.

DeSci Summit Singapore looked incredible with some fantastic talks by VitaDAO, VITAFAST and VITARNA. If you missed it, fear not - the recording can be found here.

As usual, the highlight for August in the aging world has been ARDD, which VitaDAO was proud to sponsor for yet another year. We loved the new tracks that were added on Emerging Technologies and Physics in Aging, run by VitaDAO’s own Max Unfried. In case you missed it, here is a collection of impressions and highlights from the conference by another of our contributors, Kamil Pabis.

Speaking of great conferences, Biomarkers of Aging is fast approaching. We’re always happy to support the amazing organising team and they have been kind enough to offer VITA holders 50% off and community members 30% off registration price!

The offer is only valid until September 30th, with the code, VitaDAO token holders off any ticket -  "VITADAO50". Also anyone in VitaDAO's community -  "VITADAO30".

Longevity Literature Hot Picks

Published Research Papers

Nonlinear dynamics of multi-omics profiles during human aging

This study investigated nonlinear molecular changes in aging through multi-omics profiling of 108 participants aged 25 to 75. It identified key shifts in molecular markers at around 44 and 60 years of age, linked to transitions in immune regulation, metabolism, and disease risk.

Development of an epigenetic clock resistant to changes in immune cell composition

Epigenetic clocks are influenced by the changing composition of immune cells with age. This study found that naive CD8+ T cells appear 15–20 years younger than effector memory T cells in the same individual, suggesting that current epigenetic clocks reflect both aging and immune cell composition. 

p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells

Senescent cells evade immune clearance by upregulating the immune checkpoint protein PD-L1, a process driven by p16, which stabilizes PD-L1 through inhibition of CDK4/6 and reduced degradation. Targeting PD-L1 with activating antibodies enhances the elimination of senescent cells, offering a potential strategy to improve immune surveillance and reduce age-related inflammation.

The circadian rhythm: A key variable in aging?

This study used bulk RNA sequencing across multiple organs, mouse strains, and age groups to identify common age-related transcriptional changes, highlighting circadian rhythm (CiR) transcripts as key aging markers. The CiR-proteostasis axis was central in age-associated gene expression profiles, and sex hormones were shown to influence CiR-related transcripts like Bhlhe40.

Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function

This study shows that monthly removal of p21^high cells, starting at 20 months of age, improves cardiac and metabolic function, extends both median and maximum lifespans, and enhances physical function in mice. The clearance of these proinflammatory cells reduces inflammation and mitigates age-related gene expression changes.

Age-associated clonal B cells drive B cell lymphoma in mice

Aging promotes B cell lymphoma in mice through age-associated clonal B cells (ACBCs), driven by c-Myc activation and mutations. These cells expand independently of germinal centers, fostering malignancy even in young mice. Inhibiting mTOR or c-Myc in old mice prevents pre-cancerous changes. The epigenetic changes in mouse B cells parallel those in human lymphomas.

Sport and longevity: an observational study of international athletes

This study analyzed 95,210 athletes across 44 sports and found that different sports impact lifespan variably. Pole vaulting and gymnastics were linked to the longest lifespan extension, while volleyball and sumo wrestling had negative associations. Racquet sports like tennis and badminton positively affected both male and female athletes.

HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity

This study shows that HMGA1, a chromatin protein, regulates 3D chromatin organization rather than directly activating genes. HMGA1-dense regions control gene expression, and its absence amplifies inflammatory signals during senescence. This mechanism also applies to lung cancer, highlighting HMGA1's role in chromatin structure and gene regulation.

Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis

This study found that pulsed electromagnetic fields (PEMFs) enhance angiogenesis in human endothelial cells by shifting energy metabolism from oxidative phosphorylation to glycolysis and promoting mitochondrial fission. This suggests PEMFs support angiogenesis by reprogramming energy use and altering mitochondrial structure.

Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor mutant

Disrupting the mitochondrial fission gene drp-1 extends the lifespan of daf-2 mutants by increasing mitochondrial connectivity, ATP levels, and mitophagy. Knockdown during development, but not in specific tissues, was sufficient to extend lifespan.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline

This study links infections like influenza to increased dementia risk and brain volume loss, especially in the temporal lobe. Key immune-related proteins and genetic variants were found to predict brain atrophy and cognitive decline, suggesting infections contribute to neurodegeneration.

Accelerometer-derived ‘weekend warrior’ physical activity pattern and brain health

A study of over 75,000 UK participants found that the "weekend warrior" exercise pattern, where most physical activity occurs in 1-2 days, offers similar brain health benefits to regular activity spread throughout the week. Both patterns were linked to lower risks of dementia, stroke, Parkinson’s disease, depression, and anxiety, suggesting the weekend warrior approach could be a viable option for those with busy schedules.

Short-term post-fast refeeding enhances intestinal stemness via polyamines

Fasting followed by refeeding enhances the regenerative ability of intestinal stem cells but also increases the risk of tumor formation, particularly when a tumor suppressor gene is absent. This study highlights the need for caution when using fasting-refeeding cycles in diet-based strategies, as they may inadvertently raise cancer risk alongside promoting tissue regeneration.

Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells

The release of mitochondrial double-stranded RNA (mt-dsRNA) in senescent cells triggers inflammation, contributing to the senescence-associated secretory phenotype (SASP). Targeting the proteins involved in this mt-dsRNA pathway, such as MAVS and MFN1, can reduce inflammation without affecting other aging markers, offering new potential therapies for diseases related to aging and inflammation.

Published Literature Reviews, Hypothesis, Perspectives and more

Inflated expectations: the strange craze for translational research on aging: Given existing confusion about the basic science of aging, why the high optimism in the private sector about the prospects of developing anti-aging treatments?

In November 2023, the Global Healthspan Summit in Riyadh, hosted by Hevolution Foundation, launched the US$101M XPRIZE Healthspan competition to develop treatments that rejuvenate muscle, cognition, and immunity by 10 years. This reflects growing private sector interest in anti-aging research, fueled by breakthroughs in aging science over the past 25 years.

Guidelines for minimal information on cellular senescence experimentation in vivo

Cellular senescence, marked by cell-cycle arrest and a hypersecretory state, plays roles in both tissue repair and chronic disease. To improve the identification of senescent cells in vivo, the "minimum information for cellular senescence experimentation in vivo" (MICSE) guidelines were developed, offering a standardized overview of markers across various models. 

Cell autocloning as a pathway to their real rejuvenation

The article describes geroprotection and rejuvenation methods, proposing "cell autocloning" as a potential solution to overcome current limitations. This method involves periodic autocloning of the cell nucleus, where one unstable daughter copy self-eliminates, halting cell division without physical separation, making postmitotic cells renewable. Drawing from processes like polyploidy and asymmetric division, this approach could lead to sustainable cell nucleus renewal, though significant research is still required.

Targeting multiple hallmarks of mammalian aging with combinations of interventions

Aging is caused by multiple biological processes, and targeting just one process may have limited benefits for extending lifespan. Combining therapies that address different aging pathways has shown promise in increasing lifespan, but more research is needed, as few studies have explored this promising approach.

Hallmarks of regeneration

Regeneration is a vital biological process that restores tissue structure and function after cell loss or injury, with varying capacities across species and organs. Key "hallmarks" of regeneration include activating cell sources, initiating regenerative programs, interaction with supporting cells, and regulating tissue size and function. 

Inner membrane turns inside out to exit mitochondrial organelles

The inner membrane of mitochondrial organelles flips outward to exit the organelle. How do mitochondria remove damaged sections of the inner membrane for recycling in the cytoplasm? The discovery of this exit route, where the inner membrane inverts and moves outside the organelle, sheds new light on the process.

News and Media

You’ve been lied to about ageing. Five myths debunked by science

Salk awarded $3.6 million by the California Institute for Regenerative Medicine

YouthBio Therapeutics Announces Significant Results from Joint Study with Dr. Ocampo Demonstrating Amelioration of Age-Related Cognitive Decline

New Epigenetic Clock Built on Lurking DNA Fragments

C15:0 combats cellular fragility syndrome, obesity and aging

This researcher wants to replace your brain, little by little

The secret to sleepy cells’ control of inflammatory secretions 

What accelerates brain ageing? This AI ‘brain clock’ points to answers

Resources

Need answers to complex biology questions? BioloGPT provides novel hypotheses and insights from a database of 122,038+ full papers, updated daily.

Prizes

There are just 3 months left to enter XPRIZE Healthspan!

Conferences

As conference season (and soon the year!) comes to a close, we’d like to highlight an important meeting to look forward to in November:

Biomarkers of Aging 2024

1-2 November, Boston, MA, USA

Tweets of the Month

Charles Brenner

“does that mean you missed the Pleiades meteor shower & not one time in the last 8 months did your partner wake you in the middle of the night for sex?

if you don’t value joy or surprise or intimacy, you aren’t on a journey most ppl want to be on

& btw, you are 8 mo older now”

This Tweet highlights an interesting question about balance in one’s life. Is it healthier to always be “healthy”, or do we all need to indulge in a few vices from time to time. After all, psychological well-being is also linked to improved health.

Fedichev

As some of you know, I’ve been advocating the idea that aging in humans—not mice—is driven by accumulation of long-lived forms of molecular damage. If this is the case, then to understand damage suppression, and possibly even age reversal, we need to look around at species with exceptional damage control abilities.

Pfleger

Problem: Mice die of cancer disproportionately more than humans, so lifespan results are confounded by anti-cancer mechanisms (MoAs).

How hard would it be to create a strain of mice mostly immune to cancer?

If we did, how long would they live? And what would they mostly die of?

Podcasts and Webinars

Longevity & Aging Series

NUS Medicine’s Healthy Longevity Webinar Series

A great list of Aging Podcasts

Scientists Debate How to Live Longer & Longevity Drugs | 55 - Charles Brenner

Dr. Peter Attia: Supplements for Longevity & Their Efficacy

Interview with Claude 3 Opus

Whilst all of the humans were either at ARDD or on holiday, we took the opportunity to interview Claude 3 Opus, to ask its thoughts on longevity research. 

Why do you think humans are inspired to research aging?

I believe humans are inspired to research aging primarily due to the universal desire to live longer, healthier lives. Aging is associated with physical decline, disease, and mortality, which most humans naturally wish to avoid or delay. There is also an innate human curiosity to understand the biological mechanisms underlying the aging process.

How has the longevity field changed in the last 3 decades?

Over the last 3 decades, the longevity field has seen significant advancements in our understanding of the biological processes that drive aging. This includes the discovery of longevity-associated genes and pathways, development of interventions that extend lifespan in animal models, and a shift towards treating aging as a modifiable risk factor for age-related diseases. Technological progress in areas like genomics, biomarkers, and AI have also accelerated longevity research.

What do you think have been the biggest/important discoveries in the field?

Some of the biggest discoveries in longevity research include the identification of genes and pathways that regulate lifespan, such as sirtuins, mTOR, and insulin/IGF-1 signaling. Another major milestone was the finding that calorie restriction and certain drugs like rapamycin and metformin can extend lifespan and healthspan in various animal models. The development of 'epigenetic clocks' to measure biological age has also been an important advance.

What advice would you give to people currently working in longevity research?

My advice to longevity researchers would be to embrace multidisciplinary collaboration, as the complexity of aging requires integrating insights from various fields. Prioritize translating promising findings from animal studies into humans, with a focus on interventions that compress morbidity and extend healthspan, not just lifespan. Engage proactively with policymakers, funding bodies, and the public to build support for aging research.

Which aspect of longevity research do you think requires more attention?

I believe longevity research should place more emphasis on studying aging in diverse human populations, as most findings to date come from animal models or specific cohorts. Developing multi-modal interventions that target several hallmarks of aging in parallel is another area that requires greater attention, along with understanding the role of the microbiome in aging processes.

Is aging a disease?

Whether aging is a disease is a complex question that sparks debate. Some argue that aging is a natural, inevitable process distinct from disease, while others contend that aging is the primary risk factor for chronic diseases and should itself be classified as a disease to spur medical innovation. My view is that aging is a malleable process that can be therapeutically targeted to prevent age-related diseases, regardless of the semantic debate around defining it as a disease per se.

How would you solve aging?

Solving aging will likely require a combination of approaches that address the multiple, interconnected mechanisms of the aging process. This could involve selectively eliminating senescent cells, rejuvenating stem cell populations, repairing accumulated molecular damage, epigenetic reprogramming to a more youthful state, and gene therapies targeting longevity pathways. A systems-level understanding of how these mechanisms interact will be crucial.

Do you think solving aging would facilitate humankind's efforts to colonise the galaxy?

Yes, I believe that solving aging and enabling radical life extension would be a game-changer for humankind's efforts to explore and colonize the galaxy. The immense distances and timescales involved in interstellar travel pose daunting challenges for human lifespans as they exist now. If we could maintain youthful health and cognition for centuries or even millennia, it would open up the possibility for humans to personally undertake long-duration spaceflights and oversee the development of permanent settlements on other worlds. Essentially, solving aging could be an important factor in transforming humanity into a true spacefaring civilization.

How can AI significantly influence and advance the field of aging biology?

AI has immense potential to advance aging biology research by enabling the analysis of vast datasets, such as genomic, proteomic, and multi-omics data, to uncover patterns and mechanisms underlying the aging process. AI can also accelerate the discovery of novel targets for longevity interventions, predict the outcomes of drug combinations and dosing schedules, and help develop personalized longevity plans based on an individual's genetic and physiological profile. As biological data continues to accumulate, AI will become an indispensable tool for deriving actionable insights and guiding the next generation of longevity therapies.

How can we innovate strategies that dramatically amplify human lifespan by decades or even centuries, rather than achieving mere incremental enhancements of a few years?

To achieve dramatic extensions of human lifespan by decades or centuries, we will need to think beyond the current paradigm of modest, incremental gains from drugs and lifestyle interventions. This may require harnessing radical advances in technologies like CRISPR gene editing to rewrite the human genome for extreme longevity, or leveraging breakthroughs in regenerative medicine to continuously repair and rejuvenate tissues and organs.

Nanomedicine could allow us to deploy fleets of microscopic robots to scour the body for molecular damage and fix it at the cellular level. Ultimately, if we can decode the information content of the human brain and upload it to a more durable substrate, we may be able to achieve a form of digital immortality. These are all highly speculative scenarios that face immense technical and ethical hurdles. But if we are to make transformative leaps in human lifespan, we must be willing to contemplate and rigorously investigate such seemingly science-fictional possibilities.

Outro

We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful in helping you to keep up-to-date with all the exciting longevity-related developments. See you next month!

Further Reading

On the pathogenesis of obesity: causal models and missing pieces of the puzzle

Enhanced cellular longevity arising from environmental fluctuations

The Impact of the Mediterranean Diet on Telomere Biology: Implications for Disease Management—A Narrative Review

FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species

The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review

Mechanisms of Senescence and Anti-Senescence Strategies in the Skin

Fasting and calorie restriction modulate age-associated immunosenescence and inflammaging

Enhanced cellular longevity arising from environmental fluctuations

In a recent data drop on July 26, 2024, Artan Bio shared significant progress in its innovative approach to combating genetic diseases and aging. Funded by VitaDAO ($91k) as an IP-NFT and raising over $300k through the tokenization of the Artan Bio IP-NFT, the biotech startup is developing tRNA suppressors targeting nonsense mutations linked to these conditions.

Led by CEO Anthony Schwartz and CSO Michael Torres, Artan Bio focuses on arginine mutations, specifically the CGA codon, common in proteins related to DNA damage, neurodegeneration, and tumor suppressors. Their approach aims to restore protein levels of these age-related proteins.

Initial funding enabled the development of a protein-based screening assay, leading to the design and testing of 15 potential drug candidates. Upon further testing, at least two potential lead drug candidates showed promise in correcting nonsense mutations in cells via the screening assay.

Currently, VitaRNA by Artan Bio is producing viral vectors for animal studies using AAV9, an FDA-approved gene delivery system known for its broad tissue tropism. Next steps include:

1. Generating and characterizing the AAV9 virus with lead drug candidates

2. Validating vector efficacy in delivering gene therapy and correcting nonsense mutations

3. Conducting in vivo safety and efficacy studies

4. Engaging with IP attorneys for patent strategy and filing the necessary patent applications

5. Consulting regulatory experts on clinical trial planning

The company received an update on 09/05/2024 from the contract research lab performing the experiments as mentioned above. The initial draft report clearly demonstrated that their lead candidates are active and can be packaged in a gene therapy vector. The company plans for its next funding proposal within one month to support the scale-up of the candidates for use in animal efficacy and safety studies. As Artan Bio progresses, it emphasizes community engagement while considering future funding options.

This work could open new avenues in treating genetic diseases and addressing fundamental causes of aging, promising a healthier future for all.

To watch the full data drop presentation from VitaRNA by Artan Bio, visit:

Learn more:  http://vitarna.xyz

Join the community:  http://t.me/vitarna

Coingecko: https://www.coingecko.com/en/coins/vitarna

Dear VitaDAO Community,

We're excited to share with you a recap of what was an incredibly busy summer and new opportunities that you'll soon have the opportunity to take part in.

Highlights

Funding Initiatives

• VitaRNA IPT Launch: Our community raised an impressive 300k for VitaRNA, marking our second successful IPT launch — a remarkable 10x increase from the previous IPT launch.

• TransFidelity Project: VitaDAO, in collaboration with CerebrumDAO and BeakerDAO, co-founded the TransFidelity project, contributing $50,000 to help the initiative reach its 76 ETH funding goal. This partnership aims to advance Alzheimer’s treatment by improving protein synthesis accuracy, marking a pivotal moment in on-chain science as multiple BioDAOs unite to tackle neurodegenerative diseases.

• Ab4AD IPT: VitaDAO has approved a proposal to allocate $50,000 for the development of a novel cardiovascular disease therapy at Tel Aviv University, further advancing its commitment to innovative longevity research.

• VitaDAO has been awarded 21 million BIO tokens through Bio Protocol's bio/acc rewards program. This significant allocation recognizes VitaDAO's pioneering contributions to the DeSci ecosystem and longevity research. As a key player in this ecosystem, VitaDAO is committed to contributing significantly to the progress of the broader DeSci and BIO ecosystem!

Ongoing Research Projects

• VitaRNA/ArtanBio Data Drop: Following the successful funding of the VITARNA IPT, we're excited to share the new data drop just released by ArtanBio.

New DAO Governance

• VitaDAO 2.0 Model Approved: We're very excited to announce the approval of the VitaDAO 2.0 model, marking a significant evolution in our organizational structure. This new model combines high-stake monitorship with high efficiency execution, enhancing our operational capacity and strategic alignment.

• Vitalism Organization Proposal: A proposal has been put forward to designate VitaDAO as a vitalism organization, aligning with our core values and mission.

Leadership Appointments

VitaDAO 2.0 is a new governance model that relies on Guardians, Pods (Executive Layer), and a membrane of VitaDAO contributors. This structure aims to balance mandate oversight by Guardians with autonomous execution by Pods and contributors, fostering a more agile and mission-aligned organization.

Pod leads have full accountability & autonomy for fast execution.

Guardians commit to providing audits on Pods and Pod Leads to the community to ensure alignment with VitaDAO’s mission & mandate, enhancing community’s ability to govern the DAO based on transparency and tangible KPIs.

• Genesis Guardians: We're pleased to announce the approval of our Genesis Guardians for VitaDAO 2.0: Alex Dobrin, Paul Haas, Laurence Ion, Vincent Weisser

• Pod Leads: Pod Leads will execute specific mandates within approved budgets, manage operations autonomously, and report bi-weekly to Guardians.

  • Web3 Pod: Alex Dobrin& Alex Miloski

  • Longevity Pod (Interim): Alex Miloski (4-month term)

Community Events

VitaDAO is bringing DeSci to Asia! Join us and hear from our amazing community:

Join us at the DeSci & Bio/acc Summit in Singapore, Sept 16: https://lu.ma/descisummit

Looking Ahead

As we transition to VitaDAO 2.0, we're poised for even greater achievements. Our new structure will enable us to scale our impact while maintaining the decentralized ethos that defines us.

Exciting new initiatives are brewing inside the Longevity Pod, and we can't wait to share them with you soon!

These projects will be open for community participation, offering everyone a chance to contribute to advancing cutting-edge longevity research. Stay tuned and keep an eye on us—big things are on the horizon!

Thank you for your continued support and engagement,

VitaDAO Web3 Pod

Introduction

Welcome back Vitalians, it’s been an eventful month in longevity and DeSci. 

Please join us in congratulating the TransFidelity team for passing the VitaDAO token holder vote. This proposal will allocate $50,000 to TransFidelity, a project focused on preventing neurodegenerative diseases by improving the accuracy of protein synthesis, thereby reducing the formation of harmful protein aggregates.

VitaDAO-backed Oisín Biotechnologies raises $15M Series A led by AbbVie Ventures. Oisín Bio aims to advance genetic medicines for age-related conditions, focusing on muscle-building to combat frailty.

We are also excited to share that the BIO Genesis event is underway. BIO creates a permanent, global pool of capital and talent, aiming to revolutionise biomedical science and creating a permissionless layer to back scientific projects with decentralized funding, liquidity & incentives.

This month also brings the sad news that renowned Professor Leonard Hayflick, a legend in the aging field, has passed away. We’d like to dedicate this issue to honor the extraordinary life of Professor Hayflick, a visionary whose relentless pursuit of knowledge redefined our understanding of life itself. Hayflick was not just a scientist; he was a pioneer who dared to challenge the status quo, forever altering the landscape of biology and medicine. 

For over half a century, there was a scientific dogma that human cells could proliferate indefinitely, until Leonard Hayflick performed some pioneering experiments in the early 1960s which showed this was not the case, and after a reproducible number of divisions, later coined the “Hayflick Limit” cells would permanently stop dividing. The cessation of cell division is now known as cellular senescence, and the study of this phenomenon has blossomed into a scientific field in its own right. With several papers showing genetic or pharmacological removal of senescent cells can increase lifespan in mice, there is now a huge academic and pharmaceutical effort to further understand and target this process in an attempt to improve human healthspan and lifespan.

In addition to discovering cellular senescence, Prof. Hayflick developed the WI-38 cell line which became a cornerstone of modern vaccines, safeguarding the health of billions worldwide—a testament to his enduring legacy. Furthermore, he also developed the first inverted microscope for use in cell culture research, the design of which is still used today in modern microscopes.

But Leonard Hayflick’s journey was not without its trials. He faced controversies and opposition, yet he stood firm, driven by a belief that science must serve humanity, no matter the personal cost. His courage in the face of adversity and his unwavering dedication to truth inspired generations of scientists to question, explore, and innovate. Leonard Hayflick’s life was a beacon of inspiration, reminding us all that true progress is born from curiosity, courage, and a deep commitment to making the world a better place. As we commemorate his life, we celebrate not only his remarkable achievements but the spirit of perseverance and passion that defined his work. His legacy will continue to inspire and guide us, a shining light in the ever-evolving quest for knowledge.

At the end of this newsletter you’ll find some thoughts and quotes from him as well as a few words from his esteemed colleagues and students. 

Longevity Literature Hot Picks

Preprint Corner in collaboration with

The Longevist is a preprint overlay journal spotlighting the most promising longevity studies each quarter.

Check out these latest preprints, which have all been entered into the 2Q24 longlist to be in the running to receive a coveted place in The Longevist. As always, you can refer preprints for consideration in The Longevist and the person who recommends the highest-voted preprint of the quarter will receive a prize of 200 VITA!

A combination of the geroprotectors trametinib and rapamycin is more effective than either drug alone

Inhibition of the insulin/IGF/mTORC1/Ras network, particularly through drugs like trametinib and rapamycin, can extend lifespan and improve health in mice, with combined treatment showing greater benefits than either drug alone. This suggests that repurposing these drugs for geroprotection in humans may have significant translational potential.

The Emergent Aging Model: Aging as an Emergent Property of Biological Systems

The Emergent Aging Model (EAM) suggests that aging is an emergent property of complex biological systems, such as gene networks, where aging arises at the system level even if individual components do not age. EAM explains aging as an increase in mortality rate over time and aligns with observed stochastic influences on aging, providing a framework consistent with models like the Gompertz model and applicable to various biological species.

Published Research Papers

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan

This study has received a huge amount of press attention and discussion from the scientific community. The research demonstrates that IL-11, a pro-inflammatory cytokine, negatively impacts age-related diseases and lifespan by regulating the ERK–AMPK–mTORC1 axis as mice age. Deletion or inhibition of IL-11 significantly extends lifespan and improves health in aged mice, suggesting that anti-IL-11 therapy, currently under trial for fibrotic lung disease, could potentially mitigate aging-related pathologies in humans.

An NAD+-dependent metabolic checkpoint regulates hematopoietic stem cell activation and aging

The study reveals that CD38, an NAD+-dependent enzyme, facilitates hematopoietic stem cell (HSC) proliferation in young mice by promoting mitochondrial Ca2+ influx and metabolism, but its aberrant upregulation in aged mice leads to HSC deterioration through disrupted NAD+ metabolism and impaired mitochondrial stress responses. Pharmacological inactivation of CD38 mitigates these aging effects, underscoring an NAD+ metabolic checkpoint that balances mitochondrial activity to maintain HSC function across the lifespan.

Overexpression of mitochondrial fission or mitochondrial fusion genes enhances resilience and extends longevity

This study shows that overexpressing mitochondrial fission or fusion genes in C. elegans leads to increased mitochondrial fragmentation but unexpectedly extends lifespan and enhances stress resistance, despite not maintaining a youthful mitochondrial network morphology. This suggests that enhancing mitochondrial dynamics, rather than preserving their youthful structure, is key to promoting resilience and longevity.

The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening

The study reveals a shared transcription factor binding site (TFBS) signature between aging and development, where early-life cis-regulatory elements (cCREs) lose accessibility over time, driven by a redistribution of transcription factors (TFs) towards AP-1-rich cCREs. This shift, coupled with a mild downregulation of cell identity TFs, alters gene expression, suggesting that AP-1-linked chromatin remodeling, initially promoting maturation, is later co-opted in aging to disrupt cell identity and function.

Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor mutant

Disrupting the mitochondrial fission gene drp-1 significantly extends the lifespan of daf-2 insulin/IGF-1 signaling mutants in C. elegans. This lifespan extension is linked to increased mitophagy, enhanced mitochondrial and peroxisomal connectivity, and improved energy production, while specific tissue knockdowns and ROS levels are not affected.

Obesity and risk of diseases associated with hallmarks of cellular ageing: a multicohort study

This multicohort study found that obesity significantly increases the risk of developing diseases associated with cellular aging, such as those linked to mitochondrial dysfunction, telomere attrition, and stem cell exhaustion. Obesity-related cellular aging processes contribute substantially to increased mortality, suggesting that targeting these aging mechanisms could help mitigate the health impacts of the obesity epidemic.

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo

This study introduces the CellPopAge Clock, a novel epigenetic clock designed to accelerate the discovery of anti-aging compounds by accurately monitoring the aging of human primary cell populations in vitro. The clock successfully detected slowed cellular aging when cells were treated with known longevity drugs like rapamycin and trametinib. 

Blood protein assessment of leading incident diseases and mortality in the UK Biobank

This study analyzed 1,468 proteins in 47,600 UK Biobank participants, finding 3,209 associations between 963 proteins and 21 age-related diseases. The researchers developed ProteinScores that significantly improved the prediction of 10-year disease onset compared to traditional factors. 

The correlation between CpG methylation and gene expression is driven by sequence variants

Researchers identified 189,178 regions where methylation was significantly depleted, with 41% of these regions associated with cis-acting sequence variants, termed allele-specific methylation quantitative trait loci (ASM-QTLs). Further analysis using RNA sequencing showed that ASM-QTLs largely drive the correlation between gene expression and CpG methylation. 

Effects of walking on epigenetic age acceleration: a Mendelian randomization study

Higher usual walking pace is significantly associated with a deceleration in the acceleration of epigenetic aging, as measured by four classical epigenetic clocks (GrimAge, PhenoAge, Horvath, and Hannum). However, other walking behaviors, such as walking duration and frequency, did not show a significant impact on EAA. 

Published Literature Reviews, Hypothesis, Perspectives and more

Why cancer risk declines sharply in old age

Recent research suggests that the sharp decline in cancer risk after the age of 75, particularly for lung cancer, may be linked to the role of certain genes that influence how the body ages and responds to cancerous changes. 

Why do eggs in ovaries last for decades? Long-lived proteins may be key

Mammals are born with a set number of oocytes, which can remain viable for decades. Recent mouse studies suggest this longevity may be due to ovarian proteins that last nearly as long as the organism itself, potentially supporting long-term fertility. 

Microbiota-bone axis in ageing-related bone diseases

This review highlights the crucial role of gut microbiota in maintaining bone homeostasis, particularly in the context of aging. It explores how the gut microbiota influences bone metabolism through various mechanisms, including its effects on the endocrine and immune systems and the production of gut microbiota-derived metabolites.

The complexity of coffee and its impact on metabolism

Coffee contains various bioactive compounds, including caffeine, which is metabolized into paraxanthine in the body. Paraxanthine, though not present in coffee, shares many of caffeine's effects and likely contributes significantly to coffee's impact on metabolism. While coffee consumption increases metabolic rate by 5% to 20%, individual responses vary due to factors like caffeine clearance, genetic differences, age, and body composition.

The role of cellular senescence in ovarian aging

This review examines the link between ovarian aging and the accumulation of senescent cells, as well as the potential of senolytic drugs to extend reproductive longevity. Ovarian aging, marked by a decline in ovarian reserve, leads to reduced fertility and menopause.

Senolytic Prodrugs: A Promising Approach to Enhancing Senescence-targeting Intervention

This review highlights the potential of senolytic prodrugs as a solution to the side effects of traditional senolytic therapies. These prodrugs, designed to selectively eliminate senescent cells by targeting the SA-β-gal biomarker, are categorized into galactose-modified senolytics and bioorthogonal activation approaches. The development of these prodrugs, including methods like PROTACs and photodynamic therapy, aims to safely translate senolytic therapies into clinical practice.

Job Board

David Vilchez’s lab in Cologne is recruiting a postdoc/lab manager position. The position is initially until December 2025 with the possibility to be extended until December 2032

Postdoc position in cellular senescence and age-related pathologies in Prof. Marco Demaria’s lab.

News and Media

BioAge Announces First Patient Dosed in the STRIDES Phase 2 Clinical Trial 

Evaluating Azelaprag as a Novel Treatment for Obesity in Combination with Tirzepatide

A Molecular Reason Why Exercise Fights Senescence

Cells Across the Body Talk to Each Other About Aging

‘Dream come true’: study suggests drug could extend women’s fertility by five years

Cellular Reprogramming Improves Cognition in Aged Rats

Vegan Diet Lowers Biological Age in a New Study

Resources

LongevityGPT - designed to answer any aging/longevity/health/medical questions. Check out this Tweet to get more information.

Conferences

ARDD

26-30th August, Copenhagen, Denmark

BSRA 2024

4th-6th September

Molecular and Cellular Aging Meeting in San Diego

La Jolla, CA. 10th-11th Sep 2024

9th International Cell Senescence Association (ICSA) Conference

7th - 9th November, Puerto Varas, Chile

The ICSA are offering 2 Travel Fellowships for an ECR to attend the conference.

ICSA DEI Travel Fellowship Application

yICSA 1st ECR Travel Award

The Cambridge Society of Ageing and Longevity Research term card for Michaelmas 2024 is here!

Tweet of the Month

A breakdown of the IL11 paper by Martin Borch Jensen

Podcasts and Webinars

Longevity & Aging Series

NUS Medicine’s Healthy Longevity Webinar Series

David Sinclair at the Aspen Institute

David Sinclair shared some unpublished animal study results. These include:

• Reversing Alzheimer’s symptoms: Preliminary findings suggest potential for reversing symptoms in animal models.

• Hearing loss: Animal studies indicate progress in reversing hearing loss.

• ALS (Amyotrophic Lateral Sclerosis): There's encouraging data on alleviating ALS symptoms.

• Glaucoma: Sinclair anticipates clinical trials by 2025, following positive outcomes in monkey models.

• Rejuvenating skin, kidneys, and liver: Results show signs of rejuvenation in these organs.

Additionally, the FDA has approved Tet-inducible partial reprogramming gene therapies. Life Bio is nearing clinical trials, having shown promising results in monkeys, particularly in eye stroke models (NIAON) and a glaucoma model.

What exactly is this rejuvenation paradigm called “partial reprogramming” or “epigenetic rejuvenation” that has taken the longevity field by storm

Longevity, Environmental Pollution, and Nrf2 Activation with Dr. Dushani Palliyaguru - The VitaDAO Aging Science Podcast

In memory of Professor Leonard Hayflick

Here is a collection of some of his most memorable quotes, reflecting his insights, wit, and wisdom throughout his remarkable career:

“It is astonishing to realise that the human species survived hundreds of thousands of years, more than 99 percent of its time on this planet, with a life expectancy of only eighteen years.”

"The purpose of research is to ask questions. Don’t be afraid to challenge accepted wisdom, and have the courage to defend your findings and, where necessary, to challenge accepted dogma."

"The suggestion I made that the finite lifetime of cultured normal cells relates to aging was dismissed by many as foolish, but it’s been confirmed thousands of times since, worldwide."

"Had I patented the cells, I might own the world's supply of WI-38, which would make me sufficiently wealthy to buy London, I think."

"My recollection is that while the paper was in press, our electrical freezer failed, and we lost everything."

"I put all my several hundred ampoules into a liquid nitrogen container and strapped it to the back seat of my Pontiac sedan. Two of my children sat next to it, and off we went to California."

"The cells couldn’t be patented because in the early 1960s, the patent laws in the United States and most other countries prevented patenting of living materials. So I delivered ampoules of WI-38 worldwide freely to most virus vaccine manufacturers."

These quotes capture the essence of Leonard Hayflick's character—his relentless curiosity, boldness in the face of opposition, and his enduring impact on the world of science.

Outro

We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful in helping you to keep up-to-date with all the exciting longevity-related developments. See you next month!

Further Reading and Viewing

Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons

Gut microbiome and metabolomic profiles reveal the antiatherosclerotic effect of indole-3-carbinol in high-choline-fed ApoE-/- mice

Time-restricted feeding improves aortic endothelial relaxation by enhancing mitochondrial function and attenuating oxidative stress in aged mice

Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice

Sleep is associated with telomere shortening: A population-based longitudinal study

Delighted to speak in the debate on the Gracious Speech as the new Parliament opens, and to shine a light on a field that can unlock huge benefits for Britain both economically and socially: longevity research

VitaDAO, a leader in decentralized science (DeSci) focusing on longevity research, has been awarded 21 million BIO tokens through Bio Protocol's bio/acc rewards program. This significant allocation recognizes VitaDAO's pioneering contributions to the DeSci ecosystem and longevity research.

BIO Genesis Auction Now Live


BIO Genesis link

The BIO Genesis token generation event is currently underway, offering the first opportunity to acquire BIO tokens before they become transferable in Q4 2024. Key details:

- Four rounds, with Round One allowing swaps of eligible DeSci tokens (including $VITA) for BIO

- Capped at approximately $5 million in total contributed value (depending on DeSci token prices)

- 50% of tokens claimable immediately, 50% vesting linearly over 1 year

Eligible tokens for the BIO Genesis auction: $VITA $NEURON $HAIR $GROW $ATH $CRYO $PSY $RSC

VitaDAO's Opportunities in "Science Finance" (SciFi)

As a BIO token holder, VitaDAO can now participate in governing core operations of the BIO Protocol:

1. Curation: Vote on bioDAOs joining the ecosystem

2. Funding: Engage with BIO's auction contracts for bioDAO fundraising

3. Liquidity: Participate in onchain liquidity provision

4. Bio/acc Rewards: Direct incentives for bioDAOs that reach key milestones

5. Meta-Governance: Govern a range of bioDAOs and scientific IP assets

These governance rights position VitaDAO to play a pivotal role in shaping the future of DeSci and the broader biotech landscape.

Impact on DeSci and Longevity Research

The Bio Protocol aims to create an open financial network for programmable biology, making decentralized science more liquid and accessible. VitaDAO's involvement signifies a new era in DeSci, potentially accelerating breakthroughs in longevity research.

As a key player in this ecosystem, VitaDAO is well-positioned to:

• Drive innovation in longevity research

• Create value for VITA token holders

• Contribute significantly to the broader DeSci community's progress

The BIO token serves as a gateway to DeSci, putting VitaDAO at the forefront of this revolutionary approach to scientific funding and development in longevity research.

Podcast link:

In this episode of the Aging Science Podcast by VitaDAO, we explore the connection between environmental pollution and longevity with Dr. Dushani Palliyaguru. Delve into the Nrf2 pathway, a critical mechanism for cellular defense, and discover the benefits of sulforaphane from broccoli as a potent Nrf2 activator. Dr. Palliyaguru, a renowned expert in aging and disease prevention, shares her extensive research on how environmental toxins affect health and longevity. Learn about innovative strategies to combat pollution-related health risks and enhance lifespan through nutritional interventions and scientific advancements. Join us for an insightful conversation on promoting longevity in a polluted world.

Dushani Palliyaguru – brief CV 

Dushani is an expert in aging and longevity, disease prevention and environmental health. She has over a decade of experience in scientific research and leadership at top-tier institutions in the US. Dushani completed her Ph.D. in Environmental and Occupational Health at University of Pittsburgh focusing on liver disease and cancer prevention using nutritional and natural compounds (with Dr. Thomas W. Kensler). Nrf2-mediated environmental stress response pathways was a major focus of this work. Subsequently, she completed a Postdoctoral fellowship at the National Institute on Aging focusing on metabolic and molecular biomarkers of aging and Alzheimer’s disease, and pharmacological/nutritional interventions to target these. 
Her current project:

https://www.healthsurveil.us/

Pollution, environmental exposure, health and what we can do about it 

Concerns include heavy metals, volatile organic compounds, endocrine disruptors like bisphenol a (BPA), phthalates, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkyl substances (PFAS). While the evidence is often weak for the harms of specific substances, the precautionary principle should be applied to these chemicals, commonly termed persistent organic pollutants (POPs). Because these are so persistent they might have unanticipated health effects and it might be too late when we first see warning signs of those health effects, because by then the POPs would have accumulated to very high levels in the environment and the human body. 

Dushani started her company HealthSurveil, in part, because she was fed up with the slow translation of research findings. She thinks that we have the tools available now to improve the lives of people. One of the themes of her company includes monitoring environmental exposures, e.g. to airborne pollutants. Air pollution is responsible for many premature deaths and certain aspects of lung aging, especially in Asia and in large cities across the globe. 

Nrf2 signaling, sulforaphane and other molecules 

In the podcast we discuss the mounting evidence for the health benefits of sulforaphane which is one of the best studied Nrf2 activators.  

The transcription factor Nuclear factor erythroid 2-related factor 2 (NFE2L2; often abbreviated as Nrf2) regulates a host of cytoprotective proteins, including antioxidants, heatshock proteins, metal-binding proteins and the unfolded protein response (Ibrahim et al. 2020). 

Under normal conditions, Nrf2 resides in the cytoplasm and is bound to its inhibitor, Keap1. However, when a cell is under oxidative stress, Nrf2 dissociates from Keap1, translocates into the nucleus, and binds to the antioxidant response element (ARE) located in the promoter region of many cytoprotective genes. It also promotes the hepatic detoxification of carcinogens and pollutants, linking back to our initial topic of environmental exposure. 

Nrf2 is one of the best studied putative pro-longevity pathways, although the jury is still out whether elevated Nrf2 extends lifespan in mice. Regardless, Nrf2 activation has been found to promote multistress resistance, which is a conserved trait of most long-lived animals and genetic models of longevity (Hamilton and Miller 2016). Nrf2 activity is also elevated in the liver of long-lived rodent species (Lewis et al. 2015). 

We also discuss CDDO-Me (aka Bard-Me), astaxanthin, withaferin A (found in ashwagandha and part of Protandim) and a host of other putative Nrf2 inducers. Dushani mentions that these work at very different doses. We agree that researchers should avoid creating hype around potential Nrf2 activators. If these fail, it might set back the whole field. Better to pursue solid candidates from the start like sulforaphane. The major issue, however, with the isothiocyantes like sulforaphane is their instability and lack of patent protection. Thus they are quite unattractive compounds for large studies and companies. 

Understanding zero-sum games and the geroscience hypothesis 
 
A zero-sum game or situation occurs when “an advantage for one side [is] an equivalent loss for the other”. I like using this term to describe some of the problems we face. There are many such examples pertinent to longevity research. For example, when a decrease in age-related cancer leads to an increase in age-related cardiovascular disease due to so called competing risks and Taeuber’s paradox. This may be one of the reasons why it is so hard to improve all-cause mortality with drugs that target cause specific mortality. One is also reminded of the situation with statins. There is concern that adverse effects of statins will outweigh their benefits in people at sufficiently low risk of CVD, hence no population wide recommendations have been made for primary prevention in low risk individuals, to the best of my knowledge. 

When it comes to public health policy we may also encounter such zero sum situations, although it is hard to predict which policy will lead to such an issue. We discuss this fine balance in the podcast as well. Sure, lowering lead and cadmium levels in produce is good and important. But how low do we need to go? For some chemicals there may be no safe level per se. Theoretically we should eliminate them, but at some point there will be diminishing returns to the health benefits of further reductions while the costs explode. At that point the money would be better spent on aging research or something else. 

How can we avoid zero-sum situations? The geroscience hypothesis is one out. It states that a drug that slows aging, if such a drug exists, automatically benefits all diseases and all-cause mortality, even in the healthiest of the healthy. Biologically young people tend to be more resilient against environmental exposures as well. It still remains to be seen if we can make the geroscience promise come true, but we will certainly try. 

References and further reading 

Ibrahim, Lara, et al. "Defining the functional targets of Cap ‘n’collar transcription factors NRF1, NRF2, and NRF3." Antioxidants 9.10 (2020): 1025. 

Hamilton, Karyn L., and Benjamin F. Miller. "What is the evidence for stress resistance and slowed aging?." Experimental Gerontology 82 (2016): 67-72. 

Lewis, Kaitlyn N., et al. "Regulation of Nrf2 signaling and longevity in naturally long-lived rodents." Proceedings of the National Academy of Sciences 112.12 (2015): 3722-3727. 

Introduction

Welcome back, Vitalians! This month we’re celebrating VitaDAO’s 3rd birthday! It’s been an exciting journey, and we’re thrilled to share our progress and future plans with you. In the past three years, VitaDAO has evaluated over 200 projects, funded 23, and deployed over $4.5 million USD in funding.

In June 2023, VitaDAO launched the first intellectual property token pool, offering governance to the VitaDAO community (VITA-FAST). Building on this momentum, VitaDAO has since introduced a second intellectual property token (VITARNA), marking another significant milestone in our mission.

As we look forward, we're more excited than ever about the future and our role in advancing the longevity field. The best is yet to come, and we can't wait to share 100 more birthdays with all of you!

As we celebrate another milestone, let's dive into the fiery debate that has our interviewees and experts in the field at odds: "Is aging a disease?" - our most hated question in the whole interview. The responses ranged from diplomatic nods to outright defiance, making this one of our most engaging topics yet. While some argue that aging is a natural process, others see it as a gateway to disease, begging the question—can we treat aging itself? Find a snapshot of where they clash and converge below as well as the answers from many aging scientists.

Longevity Literature Hot Picks

Preprint Corner in collaboration with

The Longevist is a preprint overlay journal spotlighting the most promising longevity studies each quarter.

Check out these latest preprints, which have all been entered into the 2Q24 longlist to be in the running to receive a coveted place in The Longevist. As always, you can refer preprints for consideration in The Longevist and the person who recommends the highest-voted preprint of the quarter will receive a prize of 200 VITA!

Neuron-type specific aging-rate reveals age decelerating interventions preventing neurodegeneration

Circadian clock disruption and lack of sleep harm cells and organs by activating the DREAM complex, which de-regulates essential cellular processes. Inhibiting DREAM restores cellular health and homeostasis despite persistent clock dysfunction, making it a potential therapeutic target for mitigating the adverse effects of circadian disruptions.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner

Nicotinamide adenine dinucleotide (NAD) is crucial for various enzymatic reactions, including energy metabolism and DNA repair, and its levels can decline significantly with age. Long-term administration of the NAD+ precursor nicotinamide mononucleotide (NMN) in mice increased activity, maintained youthful gene expression, reduced frailty, improved metabolic health in males, and extended median lifespan in females by 8.5%, without increasing cancer risk, highlighting the potential of NAD+ boosters for age-related conditions and the importance of considering sex-specific effects in studies.

Comprehensive evaluation of lifespan-extending molecules in C. elegans

The nematode C. elegans, a key model organism in aging research, is ideal for high-throughput experiments due to its short lifespan and small size, yet consensus on the most effective lifespan-extending compounds remains elusive, partly due to confounding drug-bacteria interactions. This study evaluated 16 frequently reported compounds, confirming robust lifespan extension with many and revealing some synergistic effects, while also demonstrating that several compounds extend lifespan in the fly D. melanogaster and identifying new lifespan-extending molecules in C. elegans.

Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse

The female reproductive system ages early, causing infertility and endocrine issues, with the aging ovary developing a harmful fibro-inflammatory environment. This study found that systemic delivery of the anti-fibrotic drug Pirfenidone, but not the anti-inflammatory drug Etanercept, reduced ovarian fibrosis and improved ovarian function and gene expression in mice, suggesting that modulating the ovarian environment can extend reproductive longevity.

Integrative epigenetics and transcriptomics identify aging genes in human blood

Recent studies have identified many genomic regions with age-related methylation changes, but their functional consequences remain unclear, while age-related gene expression changes have shown limited consistency across populations. By integrating high-resolution epigenetic and transcriptomic data, this study identified multi-omic aging genes in blood, which are enriched for adaptive immune functions, replicate robustly across diverse populations, and are strongly associated with aging outcomes, suggesting they may be targets for epigenetic editing to promote cellular rejuvenation.

Replicative senescence is ATM driven, reversible, and accelerated by hyperactivation of ATM at normoxia

Programmed telomere shortening limits tumorigenesis by inducing replicative senescence, which is solely triggered by the ATM kinase. This study shows that ATM inhibition can delay senescence, allow normal cell divisions in some senescent cells, and that low oxygen conditions extend replicative lifespan by diminishing ATM activity, revealing how primary human cells detect shortened telomeres and the molecular mechanisms of the telomere tumor suppressor pathway.

Circadian clock disruption engages the DREAM complex in suppressing cellular health

Circadian clock disruption and lack of sleep harm cells and organs, with mechanisms involving the DREAM complex as a key health repressor activated by clock impairment. Inhibition of DREAM restores healthy cellular homeostasis and alleviates dysfunction in clock-impaired systems, suggesting DREAM as a therapeutic target to mitigate the negative health effects of circadian disruptions.

Published Research Papers

Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule

Previously VitaDAO-funded Korolchuk lab, have published a new study in Dev Cell, showing that age-dependent downregulation of mitophagy drives senescence and cell aging - phenotypes which can be rescued by restoring mitophagy levels.

TERT activation targets DNA methylation and multiple aging hallmarks

Insufficient telomerase activity, due to low TERT gene transcription, leads to telomere dysfunction and aging pathologies. A TERT activator compound (TAC) has been identified that upregulates TERT via the MEK/ERK/AP-1 cascade, promoting telomere synthesis, reducing cellular senescence and inflammation, and enhancing cognitive function in aged mice without evident toxicity, highlighting TERT's crucial role in aging and potential therapeutic applications.

Principal component-based clinical aging clocks identify signatures of healthy aging and targets for clinical intervention

Biological age clocks should predict mortality and provide insights for healthy aging. By applying principal component analysis to clinical data, we developed PCAge and LinAge clocks, identifying signatures of metabolic, cardiac, renal dysfunction, and inflammation predicting unsuccessful aging, with potential for drug intervention impacts. These clocks, including a tailored version for the CALERIE study, show that mild caloric restriction reduces biological age, highlighting the value of integrating biological markers for preventative medicine and promoting healthy aging.

Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake

Caloric restriction (CR) in mice, achieved by cold-induced metabolism with matched protein intake, resulted in reduced body weight, lean and fat mass, leptin, IGF-1, and TNF-α levels, along with improved survival compared to ad libitum-fed mice. These findings suggest that the longevity benefits of CR are mediated by energy imbalance rather than low energy or protein intake alone.

Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial

People with peripheral artery disease (PAD) experience increased oxidative stress, impaired mitochondrial activity, and poor walking performance. A 6-month randomized clinical trial showed that oral nicotinamide riboside (NR) significantly improved walking distance compared to placebo, with NR alone improving the 6-minute walk test by 31.0 meters among those adhering to the regimen, while resveratrol did not provide additional benefits.

Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony

In aging, physiological networks decline at different rates among individuals, resulting in varied lifespans, with 70% of lifespan variance unexplained by genetics. Using Asynch-seq, a new method to study gene-expression heterogeneity, researchers created a detailed atlas of non-genetic variation in Caenorhabditis elegans, identifying the decoupling of mRNA content between germline and soma as a major source of aging variability, suggesting that targeting pleiotropic genes can reduce lifespan disparities.

Sex-dependent regulation of vertebrate somatic growth and aging by germ cells

Germ cells influence somatic growth and aging differently in male and female Nothobranchius furzeri, a short-lived vertebrate model. Removing germ cells shortened lifespan and altered estrogen and IGF-1 signaling in females, while in males, it improved health via increased vitamin D signaling, highlighting sex-dependent pathways in regulating growth and aging.

Single-cell mitochondrial sequencing reveals low-frequency mitochondrial mutations in naturally aging mice

Mitochondria are vital for many biological processes, but methods to study their heterogeneity at the single-cell level are limited. This study optimized the DNBelab C4 single-cell ATAC sequencing workflow for mitochondrial sequencing (C4_mtscATAC-seq), validated its effectiveness in HEK-293T cells, and applied it to mouse spleen and bone marrow tissues, revealing higher mitochondrial DNA content and fewer mutations in young tissues compared to aged tissues, with specific mtDNA variations linked to differential gene expression.

Epigenetic predictors of species maximum life span and other life-history traits in mammals

By analyzing 15,000 samples from 348 mammalian species, researchers developed DNA methylation (DNAm) predictors for maximum life span, gestation time, and age at sexual maturity. These predictors reveal an innate longevity advantage for females in some species, remain unaffected by caloric restriction or partial reprogramming, and show that maximum life span is determined by an epigenetic signature intrinsic to each species, distinct from individual mortality risk.

Published Literature Reviews, Hypothesis, Perspectives and more

The human gut microbiome and aging

The human gut microbiome changes throughout life, influenced by factors such as birth method, diet, environment, geography, medication, and aging, with its composition impacting aging and age-related diseases. A diverse microbiome, particularly one producing anti-inflammatory metabolites like short-chain fatty acids, is consistently linked to healthy aging globally, suggesting universal features that could be targeted for interventions to promote health and longevity.

Cellular senescence in normal physiology

Cellular senescence has been shown to contribute to the pathology of numerous age-related diseases, and thus there are numerous therapeutic efforts attempting to eliminate them. However, this perspective takes a deeper look at how senescence cells also perform a number of healthy physiological roles and thus emphasising our need to fully understand this phenomenon.

SenNet recommendations for detecting senescent cells in different tissues

As mentioned above, cellular senescence is now recognized as playing both beneficial and detrimental roles in various biological processes across species. The SenNet Biomarkers Working Group offers recommendations for identifying and characterizing senescent cells in tissues, based on a comprehensive analysis of senescence markers in 14 tissues from mice and humans, aiming to support both experienced researchers and newcomers in the field.

Therapy-induced senescence through the redox lens

Therapy-induced senescent tumor cells drive tumor recurrence and disease relapse, with reactive oxygen species (ROS) playing a crucial role in initiating and establishing this senescence. The review explores how ROS and redox dynamics influence these processes and discusses potential interventions, such as senotherapeutics, to target these pathways and reduce disease relapse.

Regulation of cell function and identity by cellular senescence

Senescent cells, accumulating during aging and various contexts like embryonic development and cancer, play key roles in pathophysiological functions beyond just loss of proliferation. The discovery of the senescence-associated secretory phenotype (SASP) revealed that senescent cells also promote gain-of-function effects, influencing cell identity and impacting pathophysiology either beneficially or deleteriously.

Gene regulatory networks in disease and ageing

Precise gene expression control is crucial for cellular homeostasis and function, with its decline contributing to age-related physiological changes and diseases. Gene regulatory networks, representing molecular interactions governing gene expression, have been inferred with high precision thanks to advances in experimental and computational technologies, aiding our understanding of cellular aging and disease mechanisms.

Neuronal senescence may drive brain aging

Senescence was traditionally thought to be a phenotype affecting proliferating cells, however numerous studies have now shown that post-mitotic cells can also undergo senescence. This perspective examines the role of senescent neuronal cells and their impact on neurological aging.

Psychogenic Aging: A Novel Prospect to Integrate Psychobiological Hallmarks of Aging

Psychological factors are crucial predictors of healthspan and longevity but are often overlooked in aging research. Psychogenic Aging, a new branch of biogerontology, aims to integrate these psychological influences into geroscience, advocating for their inclusion in the Hallmarks of Aging framework to enhance understanding and development of anti-aging therapies.

Job Board

Did you know Retro Bio offers an accelerated PhD program? 

They are also looking for a Facility Manager.

Some Hevolution funding opportunities

1. Hevolution Foundation Postdoctoral Training in Geroscience Program (HF-PTG)

2. Hevolution/AFAR New Investigator Awards in Aging Biology and Geroscience Research

3. 2024 Hevolution Foundation Saudi Arabia Postdoctoral Fellowship for Aging Biology & Geroscience (HF-SAP)

The AbuGoot lab is hiring for a number of grad, postdoc and scientist positions for exciting new projects in the aging/AI spaces. We leverage high-throughput screening tools to understand aging and AI to interpret the results, and then build new rejuvenative therapies.

Announcing COHORT 5 of the Longevity Biotech Fellowship! Join +600 hardcore engineers, scientists, entrepreneurs, investors, and operators working to solve aging. 

Apply now! 

David Vilchez is looking for a motivated postdoc to study the links between aging and amyotrophic lateral sclerosis. The project combines disease modeling using patient-derived iPSCs and C. elegans models. Apply here or contact David Vilchez directly.

News and Media

Repair Bio is harnessing gene therapy’s potential to clear excess cholesterol with a platform that could reshape cardiovascular treatment

New Drug Restores Telomerase, Improves Cognition in Mice

New Study Reveals Way to 'Significantly Reduce' Biological Age

Insilico Medicine completes patient enrollment in its Phase IIa Study in China investigating INS018_055 for Idiopathic Pulmonary Fibrosis (IPF)

Reviewing What is Known of the Aging of the Gut Microbiome

Daily multivitamins do not help people live longer, major study finds

Hevolution Foundation: Transforming Healthspan Science with Unprecedented $400M Funding Surge

Resources

People in Aging (agingbiotech.info)

Check out the who’s who of longevity research!

Available Therapeutics

A comprehensive list of interventions that are being explored to help healthy aging.

Machine learning-aided generative molecular design

Review of generative AI in small molecule chemistry

Conferences

ARDD

26-30th August, Copenhagen, Denmark

BSRA 2024

4th-6th September

La Jolla, CA. 10th-11th Sep 2024. Molecular and Cellular Aging. Registration link coming soon.

9th International Cell Senescence Association (ICSA) Conference

7th - 9th November, Puerto Varas, Chile

The ICSA are offering 2 Travel Fellowships for an ECR to attend the conference.

ICSA DEI Travel Fellowship Application

yICSA 1st ECR Travel Award

Tweet of the Month

Could Blue Zones be a hoax? 

https://x.com/DoctorTro/status/1813181976414704125

@DoctorTro

How statisticians and researchers arrived at the conclusion that the BlueZones are a FRAUD. 🤔 

🔑 Thread with key excerpts

Podcasts and Webinars

Longevity & Aging Series

NUS Medicine’s Healthy Longevity Webinar Series

Check out the latest episode of The Sheekey Science Show, where Eleanor features the top 3 preprints from the current Longevist edition.

Longevity Acceleration Podcast Episode 003 with Professor Jean Hebert of the Einstein School of Medicine

New organ system clock developed with Yale (TruDiagnostic) SymphonyAge webinar

AI For Longevity Drug Discovery: Breakthrough and Challenges Webinar

The Optispan Podcast with Matt Kaeberlein:

Anti Aging with Nutrition

Global Enlightenment? The Wild Effects Of An Age Cure

Interview flashbacks “Is Aging a Disease”

Our experts agree that aging and disease are intricately linked, but the classification of aging as a disease remains contentious. Some see aging as a natural, inevitable process, while others argue it’s the ultimate risk factor for a host of diseases. The consensus? Whether we call it a disease or not, targeting the biology of aging could revolutionize how we approach health and longevity.

Andrea Maier: “Yes! Yes, it absolutely is a disease. And we all have it!

Referring to aging as a disease might be counterproductive when communicating with the general public. However, as a physician, you require a clear diagnosis and treatment plan for your patients.

By treating the underlying mechanisms and consequences of aging, we aim to optimize the overall health and well-being of your patients. Diagnosing aging-related deterioration and assessing biological age allows you to tailor interventions and treatments accordingly. It provides a framework for addressing the physiological and pathological changes associated with aging.

In the medical field, having a clear understanding of aging and its impact on health is crucial for establishing effective practices and offering appropriate interventions to enhance patients' quality of life.”

Irina Conboy: "In my view, we notice aging specifically because tissues, organs and eventually organisms become unhealthy, e.g., it is accumulation of diseases."

David Barzilai: "Innumerable arguments have been made, with publications and conference symposium panels all focused on this issue. The answer is simple: It depends on how we choose to define aging, and how we choose to define disease. The bottom line is this: Aging biology can be argued to be the ultimate risk factor for not one, but a wide multitude of diseases. At the very least, we can observe that something in the aging process- and its molecular underpinnings- is permissive to the development of disease. Thus ultimately, if we are interested in mitigating the negative impact of disease, targeting biologic aging is a sensible approach. Precisely because biologic aging is intertwined with not one, but a wide multitude of diseases and poor health states (including frailty and lack of resilience), targeting aging biology before it deviates from the state of youth holds the potential to reduce the overall burden of chronic disease."

Matt Kaeberlein: “That’s the wrong question. It just distracts from what’s important. Aging biology is modifiable, and we can treat it to prevent disease and maintain health.”

Michael Klutstein: "No. In other words - it’s not a bug, it’s a feature."

Björn Schumacher: “Ageing is a physiological process but not a disease. However, it is the cause of all chronic diseases for which age is the primary risk factor. Therefore, we need to target the ageing process itself to prevent age-related diseases. Given the demographic change this is our only option for a future with 2 billion elderly whose active participation in society to a significant degree depends on their health. It is as urgent as fighting climate change to fight the multimorbidity that is affecting a growing proportion of the population. We need to boost ageing research now!”

John Speakman: “As far as we understand it, from an evolutionary standpoint, ageing and death happen as part of an adaptive program. We stop reproducing at a certain point in our lives, and there is no evolutionary selective pressure to invest in effective somatic maintenance programs to preserve us into old age. Mutations in genes leading to improvement in those features in later life never get passed on. Without that selective pressure to evolve physiological processes that sustain our systems they slowly fall apart. Should we call that a disease? To be honest I don’t think it matters. It is something that negatively affects all of us, creates enormous personal, economic and societal costs, and therefore there will always be an impetus to try and stop it. Interestingly the first ever written document (the story of Gilgamesh) is about discovery of anti-ageing therapeutics. We have always been interested in avoiding ageing and extending lifespan. Whether we call it a disease or not won’t change that. There is an argument that if it isn’t classed as a disease then the FDA would not grant a licence for drugs that aim to retard ageing in general, rather than specific components of it. Calling it a disease then is just a pragmatic solution to a practical hurdle. It’s not something that I think scientists should spend their time agonising over. If (when?) an effective anti-aging drug appears that needs approval, a billionaire will pay a very well paid lawyer to argue the case that ageing is a disease, and then the path will be open for FDA approval.”

Tom Kirkwood: “For me, ageing isn’t a disease in the sense I would usually apply to this term. It’s a normal process. But by its very nature it involves the generation of molecular and cellular abnormality. This feeds into multiple kinds of dysfunction. When a particular kind of dysfunction – which may have causes additional to ageing – passes a threshold recognised by clinicians, it gets a diagnosis of disease.”

Alex Cagan: “Aging certainly raises the risk for a number of diseases. Whether or not we define aging itself as a disease I would consider largely a semantics issue, though with implications for how we think about our lives and how we fund aging research. I enjoy considering different perspectives on aging, whether it is something we should ‘accept’ or ‘conquer’ or ‘cure’. Such conversations remind me of Sophocles’ lines about humanity from Antigone ‘Numberless are the world’s wonders, but none more wonderful than man; …from every wind he has made himself secure — from all but one: In the late wind of death he cannot stand.” It is awe inspiring and humbling to think that there is a realistic prospect that aging itself could be overcome through human ingenuity. Though we are currently far from reaching this point I think it’s important that as a society we begin to have conversations about what the implications of this would mean.”

Barry Bentley: "There is little agreement amongst gerontologists on how to classify aging, mainly because aging is such a catch-all term that refers to many things: biological age, as a sociological status or marker, chronological advancement, appearance, etc. Personally, I think the debate is somewhat counterproductive. Regardless of how we use the term, and whether we call it a disease, the fact remains that people become sicker as they get older. My own approach is to focus on those aspects that make people sick: the underlying aging-related pathology."

Nicole Ehrhart: "Modern medicine is based upon detection and subsequent diagnosis of a specific condition which is then treated. However, changes in our cells and tissues are occurring with the passage of time. We call this “aging”. Older bodies are made up of older cells that are less and less able to repair from the wear and tear of everyday function or damage. Subsequently, when enough unrepaired damage accumulates within an organ or body system, the system fails to work properly. We recognize this end dysfunction as a “disease”. So maybe the question is: are accumulating changes that are upstream of the onset of a disease diagnosis also part of the “disease”. My answer to this is “yes”. Aging is a modifiable process that occurs over time and we should not wait until the dysfunction is so severe so as to put a specific name on it to treat it."

David Vilchez: "Aging is a natural and progressive stage in the life cycle of any animal. However, aging is a primary risk factor for multiple diseases. The key focus lies in the potential to delay aging to enhance our quality of life and prevent multiple diseases simultaneously."

Marco Demaria: “No, aging is a condition that increases our predisposition to develop diseases.”

Adam Freund: "Whether a condition is generally considered a disease vs “normal aging” is primarily based on the prevalence of that condition in the general population: an isolated group whose members all harbor presenilin-1 mutations would characterize Alzheimer’s as “normal aging” because it would be universal. This controversy, therefore, reduces to a question of reference point (shameless plug for a thought piece I wrote on this topic). Irrespective of how we label it, aging is a process that can and should be therapeutically altered."

Vera Gorbunova: “From the evolutionary standpoint aging is not a disease. However, we have to approach it as a disease to develop treatments and interventions.”

Matt Yousefzadeh: "This is how you start a fight over beers when you get a bunch of aging researchers together. I think it is a disease, but also a natural and omnipresent condition. A very milquetoast take right? Realistically it probably sits in between the two states. Some people feel very strongly about it, but I’d rather focus on the science rather than semantics."

Tim Peterson: “I get that this matters to the FDA, but I’m not sure I have much to add to this debate other than people should have more rights to try new medicines.”

Joao Pedro de Magalhaes: "That’s a good question, but I suppose it depends on the definitions of aging and of disease. As such, I think it’s more of a semantics question than a biological one. Regardless of the definitions, aging is a trigger for diseases, and it should be targeted therapeutically."

ChatGPT: “Aging is a highly complex and multifaceted process. A plausible approach would be to tackle it from both a biological and a sociocultural angle:

‍Biologically: Focus on cellular and genetic levels. This could involve targeting senescent cells, managing telomere length, and improving proteostasis, along with employing genetic engineering techniques like CRISPR to modify or replace genes linked with aging.

Socioculturally: The intersection of technology, lifestyle, and health would have to be addressed. Integrative health systems would become a priority, where AI, human medical expertise, and regular health monitoring would ensure that people stay in the best health possible.”

Peter Fedichev: “This is a hard question that is probably more politically and emotionally charged than scientifically justified. From what we see in human and animal data, I believe aging can be slowed down and even stopped, not reversed. In this sense, this “disease” can not be fully cured but may be prevented. A huge entropic component in human aging makes aging more like a syndrome (multiple diseases leading to the same symptoms). To me, this does not matter. 

I am trying to avoid this conversation since it quickly gets murky and is dangerously close to scholastics. I believe that aging must be stopped, and once this is demonstrated, the technological solution will be covered by governments and insurance regardless of whether it addresses a disease. The potential upside is huge. It is so huge that new business models will emerge if the existing payers fail to recognize the opportunity.  If I am correct on this, we must forget about politics and focus on demonstrating an effective solution.”

Shahaf Peleg: “No, it’s worse. Studying aging is currently the second most unattainable and important quest of mankind (I’ve ranked space travel as first). Aging is more complicated, inevitable, and lacks any treatment in comparison. Moreover, it is the primary cause of a large number of diseases, and slowing down aging can delay many of them. Aging is a fundamental process that gradually 'kills' us.”

Viktor Korolchuk: “If we are ever able to delay or cure human ageing, it will become a disease from the past for generations to come.”

Outro

Thank you for being part of our journey. Here’s to another year of exploring the fascinating world of longevity research! We appreciate you sticking with our research newsletter for another month and hope the content we curate is useful in helping you to keep up-to-date with all the exciting longevity-related developments. See you next month!

Further Reading

NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype

Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age

mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process

The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases

Excessive STAU1 condensate drives mTOR translation and autophagy dysfunction in neurodegeneration

Stress-resilience impacts psychological wellbeing as evidenced by brain–gut microbiome interactions

PELI2 is a negative regulator of STING signaling that is dynamically repressed during viral infection

The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging

Testing the amount of nicotinamide mononucleotide and urolithin A as compared to the label claim

Linking Aging to Cancer: The Role of Chromatin Biology

Deep learning-based prediction of one-year mortality in Finland is an accurate but unfair aging marker

Metformin treatment results in distinctive skeletal muscle mitochondrial remodeling in rats with different intrinsic aerobic capacities

Brain responses to intermittent fasting and the healthy living diet in older adults

Mechanism and role of nuclear laminin B1 in cell senescence and malignant tumors

Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age

Senescence and tissue fibrosis: opportunities for therapeutic targeting