November 2024 Longevity Research Newsletter
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
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.
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.
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.
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
Convergent evolution of senescent fibroblasts in fibrosis and cancer with aging