November Longevity Research Newsletter

VitaDAO
14 min readDec 5, 2023

Introduction

Welcome back Vitalians and please join us in congratulating the Remedium Bio team for passing the VitaDAO token holder vote with 75.61% voting in favour! This proposal was an assessment of a regenerative medicine biotechnology company, which has developed the only dose adjustable gene therapy platform technology Prometheus™ and is currently advancing multiple assets with uncorrelated risk to Investigational New Drug (IND) approval.

Get ready for some tail-wagging news! Loyal’s latest leap in longevity science has just made history. For the first time ever, the FDA has nodded yes to a drug aimed at extending lifespans — and it’s for our furry large-breed friends!

Loyal’s LOY-001, is all about giving more years of belly rubs and fetch games to our big pooches. Though not yet in the market, this breakthrough means we’re on the brink of a huge leap forward. This breakthrough is not just a victory for Loyal but a beacon of hope for all who dream of a future where longevity is within reach.

And just when we thought we’d have to spend this newsletter talking about the unfolding OpenAI drama this fantastic news came wagging in!

And the good news don’t stop here. XPRIZE Healthspan Challenge is live! Launched at the Global Healthspan Summit in Riyadh, this groundbreaking competition aims to revolutionize aging! A staggering $101 million prize awaits the team that develops a therapy to rewind the aging clock by 20 years for muscle, cognition, and immune function in older adults.

The twist? The project needs to demonstrate remarkable results within just one year of treatment!

We also have some exciting new research and fascinating reviews. We’ve explored one of them “Epigenetic aging of mammalian gametes” more deeply with the lead author Prof. Michael Klutstein in our monthly interview!

Longevity Literature Hot Picks

Preprint Corner

The votes are in — The Longevist curators have decided what they think are the most important preprints of Q3. Before we publish the Q3 Issue of the Longevist, take a look at our previous issues!

Check out these latest preprints, each of these will be entered into the Q4 longlist to be in the running to receive a coveted place in The Longevist. They are also available to review on our reviewing platform The Longevity Decentralized Review (TLDR) for a bounty of 50 VITA per review.

As always, you can refer preprints to The Longevist and receive a bounty of 50 VITA for each one that makes the editors’ shortlist or 200 VITA if it makes the curators’ top 3.

Intranasal GHK peptide enhances resilience to cognitive decline in aging mice

Protein thiol alterations drive aberrant phase separation in aging

Regulators of health and lifespan extension in genetically diverse mice on dietary restriction

Quantification of healthspan in aging mice: Introducing FAMY and GRAIL

The AccelerAge framework: A new statistical approach to predict biological age based on time-to-event data

A mitochondria-regulated p53-CCF circuit integrates genome integrity with inflammation

Published Research Papers

In vivo reprogramming leads to premature death linked to hepatic and intestinal failure

Continuous in vivo expression of reprogramming factors (Oct4, Sox2, Klf4, c‐Myc) can reverse aspects of aging in tissues but causes liver and intestinal dysfunction, leading to weight loss and premature death. A transgenic mouse strain was created to avoid these side effects, allowing safer, longer-term rejuvenation studies.

Failure to Repair Endogenous DNA Damage in β-Cells Causes Adult-Onset Diabetes in Mice

Increased age raises type 2 diabetes risk due to DNA damage in β-cells. Ercc1-deficient mice developed diabetes, linking DNA damage to β-cell dysfunction and disease onset.

Life expectancy can increase by up to 10 years following sustained shifts towards healthier diets in the United Kingdom

Making healthy food choices can significantly impact your life expectancy. Research using data from the UK Biobank suggests that transitioning from unhealthy eating habits to recommended dietary patterns could add nearly 9 years to the lives of 40-year-old men and women, with even greater gains by adopting longevity-associated diets rich in whole grains, nuts, and fruits while reducing sugar-sweetened beverages and processed meats.

Cellular Senescence Exacerbates Features of Aging in the Eyes

Senescent ocular cells (SOCs) from human corneas exhibit increased aging markers and disrupt epithelial barriers due to a pro-inflammatory secretory phenotype (SASP). Senolytic treatment in older mice with dry eye symptoms prevents corneal opacity.

Stochasticity Explains Nongenetic Inheritance of Lifespan and Apparent Trade-Offs between Reproduction and Aging

Longer-lived female flies produce longer-lived but fewer offspring, indicating a stochastic trade-off between lifespan and reproduction. This challenges traditional views on aging, suggesting random factors rather than genetics predominantly influence lifespan inheritance and aging treatments.

Longitudinal study of traumatic-stress related cellular and cognitive aging

Accelerated epigenetic aging in trauma-exposed veterans predicts increased dementia biomarkers and cognitive decline, linking psychiatric comorbidity to neurodegeneration risk.

Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice

Restricting dietary isoleucine (IleR) improves metabolic health, promotes leanness, and controls blood sugar in young and old genetically diverse mice. It also extends lifespan, particularly in males, suggesting its potential as a geroprotective intervention.

ATAC-clock: An aging clock based on chromatin accessibility

We’ve all heard of methylation clocks, now this team have developed a chromatin accessibility clock which has a direct link to age-related transcriptional alterations, whilst also outperforming a transcription clock trained on the same data.

Mid-old cells are a potential target for anti-aging interventions in the elderly

SIRT2 transgenic over-expression does not impact lifespan in mice

This study uncovers a subset of fibroblasts and smooth muscle cells termed “mid-old status” cells in aging organs, distinct from proliferative or senescent cells, exhibiting upregulated pro-inflammatory and downregulated anti-inflammatory genes. Within the stroma, the inflammatory microenvironment induced by SAA1 negatively impacts epithelial cell stability, contributing to aging-related tissue dysfunction, but this effect can be reversed by a young cell-derived protein, SLIT2, suggesting a potential method to prevent or ameliorate aspects of age-related tissue decline.

Comparative analysis of animal lifespan

Exploring aging across a diverse range of species offers valuable insights into universal aging processes. Though recent methodological advancements enable the study of evolutionarily distant species, the broad scope introduces challenges in experimental design. In this discussion, the authors discuss these challenges, identify key issues to tackle, and offer recommendations grounded in current approaches to effectively conduct comparative aging studies spanning the animal kingdom.

Published Literature Reviews, Hypotheses, Perspectives and more

Epigenetic aging of mammalian gametes

Olfaction: an emerging regulator of longevity and metabolism

Authored by a VitaDAO fellow!

To promote healthy aging, focus on the environment

Combining geroscience with environmental research offers a way to understand and improve healthy aging and reduce health disparities, by studying how environments influence aging processes from an early age.

Entropy Meets Physiology: Should We Translate Aging as Disorder?

Multipotential stem/progenitor cells, crucial for tissue homeostasis, face age-related challenges, leading to altered self-renewal, differentiation, and immunomodulation, contributing to tissue destruction and reduced metabolic performance. This review highlights the impact of aging on mesenchymal stromal/stem cells (MSCs) and suggests a parallel between the thermodynamic concept of “entropy” and biological aging, proposing that both entail irreversible disorder within systems. The question arises: should aging be viewed as disorder?

The power and potential of mitochondria transfer

Mitochondria, traditionally considered to pass down vertically during cell division, are now recognized to undergo intercellular transfer in certain cell types, allowing them to be delivered to unrelated cell types. This process, termed intercellular mitochondria transfer, plays a role in regulating various physiological functions across organ systems. This review explores the mechanisms and impacts of intercellular mitochondria transfer on various cellular processes.

The longevity bottleneck hypothesis: Could dinosaurs have shaped ageing in present-day mammals?

The intriguing contrast in ageing patterns between mammals and certain reptiles and amphibians sparks curiosity about the evolutionary roots of ageing. While mammals, shaped by the dominance of dinosaurs over millions of years, exhibit marked ageing, some reptiles defy ageing or age very slowly. The ‘longevity bottleneck hypothesis’ suggests that the pressure for rapid reproduction during the era of dinosaurs led to the loss or inactivation of genes and pathways associated with long life in early mammals, creating an enduring impact on their ageing processes.

Job board

Maja Funk Lab at Holmholth Munich is looking for a PhD candidate on a lung organoids project to investigate the links between ageing and environmental stress in COPD, as well as a technical assistant

Maria Mittelbrunn is hiring a postdocs interested in immunometabolism during inflammation and aging at the Centro de Biología Molecular Severo Ochoa in Madrid.

PhD positions in barcelona with Dr. Ana Victoria Lechuga-Vieco on Mitochondrial Biology and Tissue Regeneration

Joao Pedro de Magalhaes has an opening for a PhD studentship at the University of Birmingham to study ageing, longevity and cellular rejuvenation

Deadline: 4th January 2024

An exciting research fellow opportunity to join the groups of Dr Nazif Alic and Prof. Linda Partridge at the UCL Institute of Healthy Ageing. The successful applicant will investigate the role of the multiple copies of tRNAiMet in animal development and ageing. Deadline: 8th December 2023.

Pankaj Kapahi has an opening for a postdoctoral fellow interested in studying “how metabolism regulates astrocyte-neuron signaling in aging and dementia.” Send your CV to pkapahi@buckinstitute.org

American Aging Association are looking for enthusiastic trainees studying aging or age-related diseases to apply for the AGE Early Career Scholar’s Program. Apply Today!

PhD Position available at University of Birmingham — Researching skeletal muscle decline with ageing and obesity: establishing a role for adipose tissue inflammation and immune system deterioration

News and Media

Venture Capital Giants In The Billion-Dollar Quest For Longevity Breakthroughs

The Secrets to Healthy Aging According to Longevity Experts

Can restoring elastin with existing drugs improve longevity?

VITALISM. n. The philosophy and movement against death and biological decline

Nature’s Design Paradox: Aging as an Inherent Software Flaw

Support the Dog Aging Project

An Aging Expert Thinks Humans Can Live for 20,000 Years. He’s Not Crazy

The Clues to Longer Life That Are Coming From Dogs

Resources

Bottlenecks of Aging by the Amaranth Foundation

The science of longevity and the quest to solve an age-old problem

Coleen Murphy’s upcoming book How We Age: The Science of Longevity tells the story of these remarkable discoveries through the words of a protagonist in this field.

Prizes

The deadline is approaching for the Longevity Funding Innovation Prize and the reward of $20000 is still up for grabs

XPRIZE Healthspan is a $101 million global competition to revolutionize the way we approach human aging.

Conferences

Dec 1–2nd, San Francisco

Foresight institute vision weekend

Dec 4th, Novato CA

The Biomarkers of Aging Symposium

Dec 5–6th, Buck Institute, Novato CA

The Longevity Summit

Dec 7th, Stanford

Bay Area Aging Meeting (BAAM)

Some of the VitaDAO team will be around all of the Bay Area aging meetings so come say hi and maybe claim some Vita swag!

Tweets of the Month

Ex Binance CEO CZ is suddenly interested in biotech:

CZ 🔶 BNB @cz_binance:

Been reading about biotech, thinking about how to use crypto to accelerate research funding there.

Keep building!

Mikhail Batin

Aging remains an enigmatic phenomenon. Despite its universal occurrence, the evolutionary rationale and molecular underpinnings of aging are not fully understood.

There are three overlapping strategies to combat aging:

1. Searching for therapies based on our current understanding of aging mechanisms.

2. Identifying new targets through big data analysis, such as transcriptomics.

3. Validating aging theories and testing them empirically…….

Danielle Beckman

What’s the biggest difference between a neuron from a young vs. an aged primate? It is not the length of the axon and dendrites, but the number of spines available to make contact and connections with other surrounding neurons!

Podcasts and Webinars

Longevity & Aging Series

Aging (Aging-US) and FOXO Technologies collaborated to produce a special video series on aging research: Longevity & Aging Series. In this limited series, selected Aging researchers were invited to speak about their research with host Dr. Brian Chen, an adjunct faculty member at the University of California San Diego. LEARN MORE

Check out some talks from The Longevity Forum’s Longevity Week

The longevity revolution has the potential to transform healthcare in our lifetime

Funding Opportunities

The SENS Research Foundation is now accepting applications for our undergraduate Summer Scholar Program and our Post-Baccalaureate program (which is paid)! Apply today

Interview with Michael Klutstein

Michael Klutstein is an Associate Professor Epigenetics who heads The Chromatin and Aging Research Lab at the Hebrew University of Jerusalem. His lab is interested in understanding the dynamics of heterochromatin adaptation and subsequent gene expression during cellular and developmental processes and how these contribute to the process of aging in different tissues

What inspired you to enter longevity research?

The future of mankind depends on our ability to successfully cohabitate with our eco system, to gain and make perfect use of experience and wisdom and to successfully colonize other planets. All these goals require that we live longer than we do today. For the future of mankind- longevity research is essential.

Which of the current theories of ageing do you think are the most convincing?

I do not currently prefer one theory as they all grasp some real aspects of aging, but in my opinion fail to grasp the picture in its entirety. I think aging is so pleotropic that more extensive theories are needed to understand it. Recently, a theory of elevated stochasticity as an origin for aging is starting to emerge. In my opinion- this is the closest thing to an comprehensive theory for aging we have today.

How has the field changed since you started?

From a couple of genes involved in aging we have dozens now. From a handful of mechanisms involved we have many. From no treatments to delay aging we have now several strong candidates.

What mistakes do you think the longevity field has made?

Too much emphasis was given to interventions instead of deep biological understanding. This is true for many other scientific fields, but I think in this case- we would benefit much more from understanding the basic Biology.

Other than your own, what do you think have been the biggest/important discoveries in the field?

I will focus on the field of reproductive aging, as this is my main focus. I would like to highlight the excellent work of Bjorn Schumacher who is developing the theory of elevated stochasticity in aging, and who has shown several key points in reproductive aging in nematodes. Also, the work of Francesca Duncan, to show how ovaries change with age have been a key to gain insight into how reproductive aging occurs.

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

Open your eyes, ears and minds, cause this field is going to explode…

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

The answer to this one is obvious as it is close to my heart- I think the field of reproductive aging is key to understanding aging in general and deserves much more attention and resources.

Is ageing a disease?

No. In other words — it’s not a bug, it’s a feature.

In your recent work, you describe how germ cells also age, similar to other cells in the body. Are there specific types of damage or aging processes that are more prevalent in gametes compared to adult somatic cells?

Yes, definitely. Germ cells seem to be much more sensitive to epigenetic changes than somatic cell types. The reasons for that are unclear, but a few possibilities are the fact that gametes are arrested in the cell cycle for long periods, and the fact that they are arrested at an unusual point in the cell cycle- after DNA replication. Another important point is regulatory chromatin processes that operate in gametes to activate parts of the genome that are germline specific- and which we do not know enough about.

It’s understood that while gametes age, the creation of a new organism effectively resets or wipes out this damage, leading to a ‘fresh start’ for the offspring. In the context of your focus on epigenetics, would you say epigenetic factors are the primary drivers of this full rejuvenation, or are there multiple processes involved? Do you plan to explore these additional processes?

Epigenetic processes are thought to be the main driver of this “reset”, since the genetic information is kept intact, and only the epigenetic information is changed in this process. An important and unknown link between the genetic and epigenetic information are mobile elements such as retrotransposons. These are activated because of epigenetic changes, and then move to other parts of the genome, changing the genetic material itself. Their propagation could be a key factor in understanding the interactions between the genetic material, epigenetics and transgenerational reset of information.

What can we learn from germline rejuvenation that could potentially be translated to human aging?

We can learn a great deal. We can learn that aging can be cancelled but relatively simple interventions. We can learn that the aging process may differ from system to system and between cell types. Still, germline rejuvenation brings up a lot of unsolved issues, both scientific and ethical that need to be addressed.

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

Mitophagy Activation by Urolithin A to Target Muscle Aging

Circulating monocytes expressing senescence-associated features are enriched in COVID-19 patients with severe disease

A Mediterranean Diet-Based Metabolomic Score and Cognitive Decline in Older Adults: A Case–Control Analysis Nested within the Three-City Cohort Study

Methylmalonic acid in aging and disease

Too big not to fail: Different paths lead to senescence of enlarged cells

Vitamin B12 emerges as key player during cellular reprogramming

Too big not to fail: Different paths lead to senescence of enlarged cells

Workshop Report — Biology of Stress Responses in Aging

Genetics of human longevity: From variants to genes to pathways

Cellular age explains variation in age-related cell-to-cell transcriptome variability

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment

Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice

COPI vesicle formation and N-myristoylation are targetable vulnerabilities of senescent cells

Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C. elegans

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Rapid measurement of ageing by automated monitoring of movement of C. elegans populations

Microautophagy regulated by STK38 and GABARAPs is essential to repair lysosomes and prevent aging

Mechanisms underlying retardation of aging by dietary energy restriction

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VitaDAO

VitaDAO is the world’s first decentralized intellectual property collective, funding and commissioning research into human longevity.