Introduction
Welcome back Vitalians! We are thrilled to celebrate our one-year anniversary of bringing you the latest research, insights, and developments in our field. Over the past year, we have covered a wide range of topics, from artificial intelligence and sustainability to genetics and aging research.
As we reflect on the past year, we are grateful for the support and engagement of our subscribers. Looking ahead, we are excited to continue bringing you the latest news and trends in our field, while also exploring new areas and expanding our coverage. Thank you for your support over the past year, and we look forward to continuing this journey with you for many more years to come.
In this edition, we are excited to feature an interview with Dr. Shahaf Peleg, a renowned expert in the field of longevity research. His insights inspired us to consider some limitations the field might be facing. Despite the increasing interest and investment in the field of aging research, it has become progressively narrower in recent times. Many scientists concentrate their efforts on traditional aspects of aging research such as diet control, physical activity, and well known longevity interventions (e.g. Rapamycin), thereby disregarding less conventional areas that have greater risk. This tendency towards conventional approaches limits funding, publication, and progress in the field, and dominant concepts are unlikely to surpass the longevity ceiling, consequently decreasing the potential impact on healthy lifespan.
To overcome this barrier, it is essential to allot more funds and attention to novel, high-risk projects that have the potential for more significant impacts on health lifespan. These undertakings may be less orthodox, but they could be the means to unlocking new discoveries that could revolutionize the field of aging research. By promoting more daring and innovative thinking, we can identify new avenues of research and discover new treatments that could help us increase healthy lifespan beyond the current limit. This requires a shift in the mindset of the research community, and greater support from funders and policymakers who understand the significance of investing in unconventional, innovative, and even risky projects that can progress the field.
VitaDAO Funded Research Projects
Congratulations to the ImmuneAge team for receiving a 99.83% majority in the tokenholder vote to secure VitaDAO funding and support.
ImmuneAge aims to rejuvenate aged hematopoietic stem cells to tackle age-related decline in the immune system, which is associated with numerous diseases due to pathological effects including chronic inflammation and loss of tumour surveillance.
Longevity Literature Hot Picks
Preprint Corner
VitaDAO’s very own longevity overlay journal - The Longevist - had its first on-chain vote to determine which preprints will receive a coveted place in the inaugural issue! Announcement of the preprints and journal launch coming in mid-May!
This month we are featuring 6 new preprints which are all available to review on our reviewing platform The Longevity Decentralised Review (TLDR) in return for a bounty of 50 $VITA each. Simply follow the above link to the TLDR page and get reviewing! What's more, we will be continuing the 50 $VITA bounty for reviewing any of the preprints featured in previous issues of this newsletter.
Development of a novel epigenetic clock resistant to changes in immune cell composition
Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction
OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced cellular
Evidence of a pan-tissue decline in stemness during human aging
Epigenetic fidelity in complex biological systems and implications for ageing
Published Research Papers
Ageing-associated changes in transcriptional elongation influence longevity
This Nature study found acceleration of RNA polymerase II (Pol II) is linked to aging and shorter lifespan as it becomes less precise and more error-prone with age. Mutations in insulin-signaling genes and low-calorie diets can slow down Pol II speed and increase lifespan. The study establishes a causal connection between Pol II speed and lifespan.
Dedifferentiation maintains melanocyte stem cells in a dynamic niche
Why does our hair turn grey with age? We know that it’s due to failure of the melanocyte stem cell (McSC) system, however the Ito lab has provided a mechanistic explanation as to why this happens. Unlike other stem cell populations, McSCs can switch between two different states (stem and transit amplifying) and have motility to travel between different compartments. However, some cells lose this motility, fail to dedifferentiate and melanocytes numbers diminish leading to a loss of pigment.
A population of stem cells with strong regenerative potential discovered in deer antlers
Numerous animals such as lizards and lobsters have significant regenerative capability whereby whole limbs can be regrown, whereas regenerative capability in mammals is rare and less extreme, for example mice can only regenerate digit tips. However, deer have an amazing capability to regenerate their antlers each year, which the Qiu lab show is due to a population of cells called antler blastema progenitor cells (ABPCs). Interestingly, mice have a similar cell type in their regenerative tip.
Biological age is increased by stress and restored upon recovery
A study showing biological age - as quantified by transcriptomic, metabolic and epigenetic readouts - can increase as result of stresses such as heterochronic parabiosis in mice, or severe COVID-19 infection, which can then revert back following cessation of the stress and recovery.
Lung adenocarcinoma promotion by air pollutants
Research showing that air pollutants contribute to lung cancer by eliciting an inflammatory response resulting in macrophages releasing the cytokine interleukin-1β, which in EGFR mutant lung alveolar type II epithelial cells can induce a progenitor-like state that drives tumourigenesis.
It has been shown that lowering body temperature can extend lifespan in numerous organisms such as nematode worms and fruit flies. The Vilchez lab now show that this effect is dependent on a protein involved in proteasome activation, which can allay age-associated protein aggregation. Interestingly, we recently featured research from John Speakman showing that body temperature impacts lifespan more than metabolic rate in 2 small mammals. Could these two findings be connected?
We experience an age-related decline in immune function which can lead to chronic systemic inflammation, which is associated with numerous diseases. Here the Goronzy lab provide a mechanism whereby the proton pump V-ATPase is targeted for degradation, leading to faulty lysosomes and subsequent accumulation of amphisomes which undergo extracellular release of their mitochondrial DNA-containing cargos, which then elicit an immune response.
A bioartificial liver device employing human-induced hepatocytes has shown promise in treating post-hepatectomy liver failure in both animal and human studies. The treatment was well-tolerated and improved liver function, suggesting it could expand the population of eligible patients for liver resection.
Engineering longevity—design of a synthetic gene oscillator to slow cellular aging
By rewiring an endogenous toggle switch, sustained oscillations were created that increased the cells' lifespan by delaying the commitment to aging. This study provides a foundation for designing gene circuits that slow aging.
CRISPR-activated expression of collagen col-120 increases lifespan and heat tolerance
sgRNAs fed to C. elegans to CRISPR-activate the expression of collagen col-120 and col-10 in adulthood increase lifespan and heat tolerance. Results suggest collagen enhancement may promote longevity and stress resistance.
New evidence that cellular aging is fundamentally controlled by mitochondrial function.
This study identified a common mechanism that regulates lifespan by controlling cytosolic ribosomal protein abundance, actin dynamics, and proteasome function through mitochondrial genes.
300,000 participants study found that being overweight didn't increase mortality risk, but obesity did, though the risk decreased with age. Additionally, lean mass didn't reduce mortality risk.
Spurious intragenic transcription is a feature of mammalian cellular senescence and tissue aging
Aberrant transcription occurs during cellular senescence and mouse aging, impacting cellular health and signal transduction pathways. This suggest that age-related spurious transcription promotes a noisy transcriptome and degradation of coherent transcriptional networks.
Published Literature Reviews
No rest for the wicked: Tumor cell senescence reshapes the immune microenvironment
Mitigating age-related somatic mutation burden
Recent clinical trials with stem cells to slow or reverse normal aging processes
Targeting the biology of aging with mTOR inhibitors
Job board
Retro biosciences are hiring across the board from fellows and research associates to project managers
Retro are focusing on Cellular reprogramming, autophagy, & plasma-inspired therapeutics.
Rubedo are looking for Director of Program Management and Portfolio Strategy
Rubedo works on innovative therapies engineered to target cells which drive chronic age-related diseases and their drug discovery platform has engineered novel first-in-class small molecules designed to selectively target senescent cells.
Calico is now accepting applications for postdoctoral fellowships
They have openings across Protein Biochemistry and Structure Biology, Lung Homeostasis and Aging, Immuno-Oncology, and Mechanisms of Yeast Aging
Buck Institute for Research on Aging, Novato, California
The Lapierre Lab is looking for motivated Ph.D. students and postdoctoral researchers!
To study how nucleo-cytoplasmic protein partitioning affects proteostasis, autophagy and aging using C. elegans.
News
People are taking a cheap drug to try reverse-age their ovaries — and cheat their 'biological clock'
Human trial - rapamycin for reproductive aging
King’s College and the LSF partner to advance human longevity education and research
Introducing the Time Initiative with AFAR are empowering undergraduate leaders in aging research
FDA approves Biogen’s ALS drug tofersen, paving new road for accelerated pathway in neuro diseases
Drs. Sinclair, Huberman, and Brenner on the Future of NMN After the FDA Ban
Experimental Alzheimer’s drug slows cognitive declines in large trial, drugmaker Eli Lilly says
The antibody therapy in stage III clinical trial improved cognitive and functional decline by 35%
Longevity Investors Conference to showcase promising startups to high-net-worth investors
Resources
Computational Biology of Aging coursebook
The course covers computational biology methods for studying aging and offers hands-on experience in analyzing gene expression, constructing aging clocks, and using dynamical systems modeling to study the biology of aging.
Articles
Humans Can Stop—But Not Fully Reverse—Aging, Study Suggests
Why don’t whales get cancer? Cracking one of medicine’s greatest mysteries
Longevity for companion animals: why should we care
Possible ‘Steps’ to Revealing Super-Agers
The “stepping stone” approach to getting longevity drugs to market
Longevity is a dish best served cold
Ageing studies in five animals suggest how to reverse decline
Boosting body’s antiviral immune response may eliminate senescent cells
Benefits of 'zombie' cells: Senescent cells aid regeneration in salamanders
The science of reversing aging
Moderate Drinking Doesn’t Lower Mortality
Longevity Seekers Embraced This Drug. But Does It Actually Fight Aging?
Improving longevity literacy – and why digital health is the answer
“We Have 30 Extra Years”: A New Way of Thinking About Aging
Rapamycin's Role as a Molecular Brake for Cellular Hyperfunction and Runaway Cells
Women In Longevity And The Renaissance Of The SENS Research Foundation
The tech entrepreneur betting he can get younger
Conferences, Workshops and Webinars
Meet the most inspiring speakers and experts gathering to discuss their present research.
Pop-up city - Zuzalu
Longevity Events in May
May 6-9th: Longevity 0-1
May 13-14th: Longevity Industry Talks
The 2023 Harvard/Glenn Symposium on Aging
22nd of May, virtual
19-20th June, University of Birmingham
5th World Aging And Rejuvenation Conference
July 17-18, 2023 in Frankfurt, Germany.
BSRA Annual Scientific Meeting
British Society for Research on Ageing is pleased to hold its 2023 annual meeting at the University of Westminster
DGfA (German Society for Research on Aging) Annual Meeting
June 29-30th, 2023 at the Volkshaus Jena.
The Groningen-Jena Aging Meeting "G-JAM" 2023
28-30th September 2023 at the European Research Institute for the Biology of Ageing (ERIBA) in Groningen, the Netherlands.
Awards and Competitions
50 000 CHF for the winner
Deadline for applications: 30th of June
The Longevity Prize announces the winners of the Hypothesis Prize!
Tweets
Thought-provoking:
Controversial:
Books
Taking us to the cutting edge of the new frontier of medicine, a visionary biotechnologist and a pathbreaking researcher show how we can optimize our health in ways that were previously unimaginable.
Outlive: The Science and Art of Longevity
“A groundbreaking manifesto on living better and longer that challenges the conventional medical thinking on aging and reveals a new approach to preventing chronic disease and extending long-term health, from a visionary physician and leading longevity expert.”
Podcasts and Videos
What they thought of aging in 1931 - The Sheekey Science
What did scientists think about aging in 1931? That’s right. 1931, because that is the year the first biological textbook was published “The Science of Life”.
NewLimit are aiming to extend human lifespan, here is a progress update
Interview with Dr. Shahaf Peleg
Dr. Shahaf Peleg is a group leader at the FBN Institute at Dummerstorf, Germany, where he focuses on studying the role of metabolism-epigenetics connectivity during early aging, response to stress, and cognitive impairment. Through his research, Dr. Peleg aims to identify new and innovative therapeutic avenues that can help increase healthy human lifespan.
What inspired you to enter longevity research?
When I was in high school, I was thinking about what I should do later in life. Should I become a lawyer? Politician? Businessman? But the more I thought about it, the more vain it seemed. I wanted to tackle an interesting challenge in life that would make a difference. Studying aging immediately popped up in my mind as such an (impossible) challenge. Also, I noticed with sadness that people age and die and I knew from a young age that I would go on one day to study aging.
Which of the current theories of ageing do you think are the most convincing?
To be honest, I believe that a truly convincing theory of aging has yet to emerge.
How has the field changed since you started?
To put it in perspective, When I started my Masters in 2006, there was already an increasing interest in researching aging, leading to more investment, funding, and conferences in the field.
Advancements in technology, such as CRISPR, advanced omics, AI, and novel drugs, have also enabled more efficient aging research. Also, the rapid development of the internet and applications such as Twitter have facilitated collaborations among scientists and enable them to interact more efficiently than before.
We also observed that many scientists have started to question previous assumptions, results, and theories on aging, which were previously published, and this is followed by heated debates. As the field of aging grows and we collect more observations, it is likely we will disprove more previous theories on aging.
Unfortunately, the field has surprisingly become narrower. A handful of concepts such as diet, exercise, rapamycin, mtUPR, and a few others have become dominant – so dominant that they are over-studied, over-published, and importantly, over-funded. This poses dual disadvantages by inhibiting other promising ideas to be studied/funded/published and by the fact that it is likely that the current dominant ideas will not break the glass ceiling of longevity.
What mistakes do you think the longevity field has made?
I have alluded to it in the previous point. The field is too narrow and it’s easier to get funded and publish if the scientist chooses a ‘safe’ canonical aspect of aging research such as caloric restriction. But this is not the way to go. We need to encourage risky projects, out-of-the-box ideas and younger researchers (not always the big names). If we really wish to have a fair chance to increase life span beyond 120, the field needs to also pursue such novel ideas – the current canonical ideas may increase healthy lifespan, but unlikely to bring us beyond the 120 mark.
It is also concerning that some of the so-called-established results (leading to theories of aging) were based on data that is not reproducible. Considerable time, effort, and money were invested in follow-up studies, which resulted in failures and even discredited the field of aging to some extent. This may have been due to researchers taking other labs' results for granted without sufficiently questioning and thoroughly reproducing the published data.
Other than your own, what do you think have been the biggest/important discoveries in the field?
Naturally, the study by Cynthia Kenyon in 1993 showing that aging can be genetically modulated really pushed the field forward. I think many discoveries are important and big in the field, and it’s hard to pick just a few. However, I do find Darren Baker's work on targeting senescent cells interesting, and I believe the research on drugs such as Rapamycin and Metformin is crucial as they show potential in increasing healthy lifespan. Additionally, Alex Zhavoronkov's work on using AI to intervene with aging is novel and may be critical for the future of the field, as it's possible that AI could better assess the enormous amount of factors that contribute to aging. Nevertheless, there are many important discoveries in the field, and only time will tell which ones are promising.
What advice would you give to people currently working in longevity research?
To stay open-minded, respect the opinions of other colleagues (even when they differ from yours), be bold, think outside the box, and don't give up when things don't work. Longevity research is challenging, but that's precisely why we do it.
Which aspect of longevity research do you think requires more attention?
More attention should be given to data reproducibility and increasing funding, particularly for risky projects.
Is ageing a disease?
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.
Your research covers a broad range of topics, including epigenetics, metabolism, and various dietary interventions. What is the biggest impact of consuming certain foods and drinks on epigenetic age?
While I am not certain about the impact of epigenetic age (and in fact, what epigenetic age tells us in terms of aging really), maintaining a healthy diet and exercising regularly can significantly improve your healthy lifespan and delay the onset of certain diseases. However, it is important to note that these practices alone may not extend lifespan beyond the 120 mark.
Your latest study used optogenetics to increase mitochondrial membrane potential in C. elegans. Can you explain the basics of optogenetics and how you were able to use this technique to modulate mitochondrial function? Do think your finding might have translational potential in the context of human aging and longevity?
I'll start with the second question - yes, I think it has potential for translation to human aging, otherwise, I wouldn't be interested in it. Our goal is never to make yeast/worms/flies/fish/mice live longer - we always aim for human aging!
I'll leave the explanation of basic optogenetics to more qualified researchers. What we're doing is not really modulating mitochondrial function or even classical optogenetics in that sense. The idea, at least from my current view, is that we use an engineered light-activated proton pump and place it inside the mitochondria. This tool was developed by Brandon Barry at Andrew Wojtovich's lab. By taking this approach, we enable animal cells to harness the energy of light into chemical energy. We theorize that this can lead to several benefits in terms of aging. For example, it's currently assumed that mitochondrial function declines with aging, and as such, our approach may compensate for impaired metabolic function and increase cellular energy levels simply by exposure to light. Please read our Nature Aging paper that we published earlier this year. We're just at the beginning, and time will tell if this risky idea will work for us.
Looking ahead, what are your upcoming research projects or collaborations that you are particularly excited about? Can you give us a sneak peek into the direction of your future work?
I would like to continue the optogenetics project as I am very excited about its potential. As for a sneak peek… I would like to start a company!
Outro
Thank you for staying with us till the very end and as always we encourage you to reach out to us about content you’d like us to discuss in our next issues. See you next month!
Further Reading
Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis
A hyper-quiescent chromatin state formed during aging is reversed by regeneration
Compartmentalization of the SUMO/RNF4 pathway by SLX4 drives DNA repair
Rhythms in barriers and fluids: Circadian clock regulation in the aging neurovascular unit
Effects of intermittent fasting on cognitive health and Alzheimer’s disease
Brain insulin responsiveness is linked to age and peripheral insulin sensitivity
Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress
Flow Cytometry-based Method for Efficient Sorting of Senescent Cells
A p21-GFP zebrafish model of senescence for rapid testing of senolytics in vivo
The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent
Reviews
Exploring the Causal Relationship Between Telomere Biology and Alzheimer’s Disease
Gene Therapy Strategies Targeting Aging-Related Diseases
Fungi as a source of bioactive molecules for the development of longevity medicines
Obesity: an evolutionary context
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