Introduction
Hi Vitalians, greetings from Vitalia. You might have heard about the city of life in Roatan, Honduras.
VitaDAO hosted a Life Extension Conference, held from February 23 to February 25, 2024, in the pop-up city of Vitalia, Honduras, was a profound journey into the future of human longevity. Nestled within Próspera's special economic zone on the idyllic Roatán Island, Vitalia emerged as a beacon of innovation, drawing inspiration from the visionary minds of Vitalik Buterin and Balaji Srinivasan. This unique event attracted over 200 attendees from around the globe, uniting them in a shared vision for a future where extended healthspan and lifespan are not just possible but expected. With a collective eye towards decentralized cities of longevity, speakers and participants alike embraced the notion of these new frontiers in the eternal quest for a longer, healthier life.
Vitalia's existence represents more than a transient assembly. It serves as a foundational step towards the creation of permanent districts dedicated to longevity, poised to fundamentally transform the biotech landscape. The special economic zone of Prospera in Roatán has a legal environment that is conducive to medical freedom and pioneering work, setting an exhilarating stage for progressive dialogues. This year's gathering not only underscored the symbiotic relationship between urban planning and health but also brought to light emerging biological research and the future of medical practices.
Projects such as Vitalia are at the forefront of accelerating longevity therapeutics development. Currently, aging is not officially recognized as a disease indication for clinical trials, raising the question of how aging should be classified. The debate is polarized; some firmly argue that aging is indeed a disease, while others strongly disagree, with many viewing the debate as a distraction from the primary goal of trying to understand and treat the age-related pathologies. This month, we're thrilled to bring you an interview with Dr. Barry Bentley, who received an Impetus Longevity Grant to explore this every topic. Enjoy!
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 will be entered into the 1Q24 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.
Most axonal mitochondria in cortical pyramidal neurons lack mitochondrial DNA and consume ATP
Published Research Papers
Targeting senescent cells in the retina with UBX1325, a senolytic drug, reduces damage in diabetic macular edema (DME). This approach, shown to be safe in a phase 1 trial, offers a potential new treatment strategy for DME, necessitating further research for validation.
The study introduces a novel approach for diagnosing progeroid disorders by developing a 'progeria phenome' and a machine-learning classifier available at https://www.mitodb.com. It also identifies new associations between certain diseases and progeroid syndromes, enhancing our understanding and diagnosis of premature aging conditions.
Wealth Redistribution to Extend Longevity in the US
A study linking wealth inequality to survival rates in the US suggests redistributing wealth could increase median longevity by up to 2.2 years, potentially aligning US mortality rates with OECD averages. Simulations indicate that policies promoting wealth equality, including those inspired by Japan's distribution, minimum inheritance, and baby bonds, could significantly reduce survival disparities.
The New England Centenarian Study identified unique protein signatures in centenarians, suggesting that despite acquiring aging markers similar to those in younger, shorter-lived individuals, they do so later in life. The study highlights specific serum proteins associated with senescence and longevity.
This research reveals that plasma membrane damage (PMD) leads to cellular senescence, contributing to aging. In budding yeast, PMD was linked to shorter lifespans, but lifespan extension was possible by upregulating membrane repair mechanisms. In human fibroblasts, PMD induced senescence through the Ca2+–p53 pathway, with upregulation of repair factor ESCRT-III mitigating this effect.
Genome-wide profiles of DNA damage represent highly accurate predictors of mammalian age
Recent advancements in genome-wide mapping techniques for single-strand breaks and abasic sites in DNA have enabled the discovery of precise age-related genomic patterns of DNA damage in mice. These patterns offer superior age prediction accuracy compared to traditional transcriptome analysis, focusing on a select group of genes.
Inhibiting TORC1 with rapamycin extends lifespan across species, a process mediated by S6K. In Drosophila, S6K activation in the fat body negates rapamycin's benefits, affects lysosome structure, and reduces inflammaging, linked through Syntaxin 13. Gender differences in inflammaging response to rapamycin were observed, with significant effects in females but not in males.
Published Literature Reviews, Hypothesis, Perspectives and more
Cellular senescence: Neither irreversible nor reversible
Cellular senescence, traditionally viewed as irreversible, might under certain conditions be transient. They suggest that senescence is a variable journey, not a permanent state, and cells can potentially return to the cell cycle, entering a distinct post-senescent phase with unique functional and clinical outcomes.
Targeting ageing with rapamycin and its derivatives in humans: a systematic review
Rapamycin and derivatives benefit immune, cardiovascular, and skin aging with no significant impact on endocrine, muscle, or nerve systems, and unassessed effects on other bodily systems. While safe in healthy individuals, they increased infections and cholesterol in those with age-related diseases, indicating a need for further and long-term studies.
Validation of biomarkers of aging
Efforts to identify omic-based biomarkers for biological aging aim to predict health outcomes and assess anti-aging interventions. However, a unified approach for validating these biomarkers before clinical use is missing. This review discusses the validation challenges and proposes recommendations to improve the process.
Missing centenarians are an international concern
Job Board
Loyal is looking for a Chief of Staff! Loyal aims to help dogs live longer and maintain their quality of life as they age, hoping to do the same for humans one day.
The Kapahi lab is seeking postdocs for an eye aging and neurodegeneration project using flies and mammals. For questions regarding this position, please email Pkapahi@buckinstitute.org or visit the website.
Postdoctoral Positions available at Brown University Center on the Biology of Aging (BoA). A list of participating investigators and detailed descriptions of faculty research programs can be found on their website
Assistant or Associate Full Professor of Geroscience positions at UCSD:
Assistant Professor - (Tenure-track): Apply
Associate or Full Professor - (Tenured): Apply
News and Media
Caloric Restriction Extends Reproductive Lifespan in Hens
Why age matters when it comes to cancer
Resources
Reproductive aging resources - compiled by Carol Magalhaes.
Prizes
Longevity Prize Million Molecule challenge with Ora Biomedical
Propose interventions to extend C. elegans lifespan, with a chance to win a prize for the most effective approach. Ora Biomedical has developed the WormBot-AI platform, combining robotics and AI to study longevity in C. elegans, a model organism for aging research. This technology enables quantitative assessment of lifespan and healthspan on a large scale, advancing our understanding of longevity.
Biomarker Challenge, our open-science competition rewarding folks who can best predict chronological age, survival/mortality and multi-morbidity incidence using biomarker data. Challenge officially begins March 1st.
Developing and validating aging biomarkers for clinical trials is challenging due to data limitations and collaboration barriers between scientists. To address this, Biolearn, an open-source toolset, was created. It harmonizes omics datasets and calculates existing aging biomarkers. More about Biolearn:
Biolearn, an open-source biomarker validation library and platform enabling easy and versatile analyses of biomarkers of aging data.
Biolearn is a tool that simplifies the analysis of biomarkers of aging data. It allows users to easily import data from publicly available sources like the Gene Expression Omnibus, National Health and Nutrition Examination Survey, and the Framingham Heart Study. Biolearn also includes reference implementations for common aging clocks such as the Horvath clock and DunedinPACE, which can be run with just a few lines of code.
Join Biolearn Discord.
Conferences
April 08-09, 2024
Valencia, Spain
5th Annual MAC Aging Research Symposium
April 28 – 30, 2024
Columbus, OH, USA
May 8 - 9, 2024
Lisbon, Portugal
The Rejuvenation Startup Summit 2024
May 10-11, 2024
Berlin, Germany
Tweet of the Month
Why has menopause become a normal part of every woman's life, when it causes unnecessary suffering?
Why is reproductive aging research still significantly underfunded when half of the population experiences menopause?
I believe this *needs* to change, so I wrote a piece about how to delay menopause to extend longevity.
Podcasts and Webinars
NUS Medicine’s Healthy Longevity Webinar Series
A great list of Aging Podcasts
80,000 Hours Podcast - Laura Deming on the science that could keep us healthy in our 80s and beyond
Matt Kaeberlein’s new podast covering a variety of topics related to longevity and healthspan - An introduction to the study of RAPAMYCIN
How this tiny mutant mouse lives so, so long
Interview with Barry Bentley
Dr Bentley is the Head of the Bioengineering Research Group and Bio-AI Laboratory at Cardiff Metropolitan University. His current research focuses on the development of laboratory systems for cryopreservation, and the development of classification and staging systems for age-related pathology within the context of the WHO ICD-11.
What inspired you to enter longevity research?
I have been fascinated and unsettled by ageing, probably for as long as I have been aware of ageing as a concept; however, I can pinpoint the exact moment I became interested in longevity as a topic of scientific research. In early 2006 I was travelling around China and teaching English on a gap year before starting university. One night, I found myself in a dimly lit internet café on the outskirts of Wenzhou city, where I was browsing through forums on science and technology to pass the time. I stumbled across a link to an article discussing the Methuselah Foundation, which led me down the rabbit hole into the world of ageing research. The prospect of slowing or even reversing biological ageing was and still is a radical idea, sounding, to some, like a concept straight out of science fiction. The realisation that there were people who were seriously working on such a seemingly intractable problem captured my imagination. I already knew at that point that I wanted to become a research scientist, but that was the nudge that shifted my focus to the biological sciences, and ultimately led to my current career.
Which of the current theories of ageing do you think are the most convincing?
Each theory has its proponents, and various degrees of evidence supporting them. With the incredible progress that has been made in developing robust epigenetic clocks, the field seems to have shifted in favour of programmed theories of ageing in recent years. With how complex biology is, and how much is still unknown, I personally think it would be a mistake to commit to any one view or theory of ageing at this point; in fact, I would not be surprised if we find that all of the main theories are true to varying extents, with ageing being a highly heterogeneous process. To inelegantly coin a phrase: I suspect there is more than one way to age a cat.
How has the field changed since you started?
The biggest change has undoubtedly been the amount of interest in the field, and consequently, the amount of investments now being made in longevity research. Whether that is because the problems of an ageing population are finally starting to become too profound to ignore, or the science has reached a level of maturity that is finally investible, society as a whole is starting to take note.
What mistakes do you think the longevity field has made?
Until recently, the longevity field – as distinct from the broader field of ageing research – had serious credibility issues, which it still has yet to completely rid itself of. Starting as a fringe area, it unfortunately became associated with some questionable groups: unscrupulous people selling snake oil, biohackers doing questionable self-experiments, and futurists who were making predictions with little consideration for the realities of research. The field did a poor job of distancing itself from the more unsavoury ideas and actors. The strength of the science now speaks for itself, but reputational damage remains.
What advice would you give to people currently working in longevity research?
Like all areas of research, the main advice I would give is to be open minded. We do not yet know which approaches will be required to effectively slow or reverse ageing – there is just too much that we don’t yet know. To make progress, we’ll need to continue asking questions, trying new approaches, and robustly challenging our assumptions.
You were awarded an Impetus grant to explore how ageing should be classified. Why is this important?
That’s a great question. Before I answer, let me give some context to how the project came about: In 2016 and 2017, my collaborator, Dr Stuart Calimport, and I were discussing our frustrations that even though the scientific understanding of ageing was rapidly improving, the science was not filtering down to the bedside to influence the way patients were treated. Part of the reason for this, we realised, was due to clinical classifications.
The World Health Organization (WHO) maintains a standard list of clinical codes, known as the International Classification of Diseases (ICD), which are used as the standard terminology by all WHO member states. These are used for recording diagnoses and treatments, for statistical and epidemiological purposes, for healthcare resourcing, approving clinical trials, medical billing, and so on – in short, they are at the core of virtually everything that happens within a health system.
Unfortunately, classifications for ageing-related changes are extremely limited in the ICD, which limits the ability to accurately describe and address ageing-related pathologies. As the idiom goes: you can’t manage what you don’t measure; and the ICD does not currently have the capacity to describe, and thus measure, ageing-related pathologies. Some groups have proposed to work around this by classifying ageing itself as a disease, but not only is this contentious, it also fails to address the heterogeneous nature of ageing – different organs and tissues age in different ways, and I believe we need the ability to capture this.
We had initial success in getting ageing recognised as a cause of disease by the WHO in 2019 [1], following which we published a large multi-author paper in Science proposing a consortium to develop a comprehensive and systematic classification system for ageing-related pathologies [2]. Norn Group thankfully saw the value in this, and awarded us an Impetus Grant to make it a reality. So far, we have recruited approximately 300 experts, who we are working with to develop these new classifications.
[1] https://doi.org/10.1089/rej.2019.2242
[2] https://doi.org/10.1126/science.aay7319
You recently hosted a consensus meeting to define the criteria for an ageing-related pathology, could you give us the highlights of this meeting?
This was the first meeting of the consortium to develop the classifications for ageing-related pathologies. Of course, to develop those classifications, it is essential that the consortium members have agreement on what constitutes an ageing-related pathology – so this was the main goal of the first meeting: to define the criteria that will allow us to differentiate an ageing-related pathology from others. We had a wide range of input from clinicians and scientists, but there was pretty much unanimous support for three criteria that were proposed: Firstly, that the damage must develop or progress with increasing age; that it should be associated with, or contribute to, functional decline or increased susceptibility to functional decline; and that, for the purposes of clinical classification, it must be based on evidence from studies in humans.
Our consortium coordinator, Dr Emma Short, who is a consultant histopathologist and research associate, did a brilliant job of chairing the meeting, and is working on writing-up the outcome of the discussions, which we will be publishing in the near future.
Is ageing a disease?
There is little agreement amongst gerontologists on how to classify ageing, mainly because ageing 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 ageing-related pathology.
What are you currently working on in the lab?
In addition to my work classifying age-related pathology, I am fortunate to have received a Fulbright Award, which is enabling me to work at Harvard Medical School and Massachusetts General Hospital this year on the development of new technologies for the cryopreservation of cells, tissues, and organs. It has been an ambition of mine for a long time to make contributions in this area, so it’s exciting to finally be making that a reality.
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!
This time we’ll leave you hanging, waiting for some exciting developments on our Members Portal. VitaDAO will soon enable $VITA holders to stake their tokens in exchange for health products and services. Keep an eye out!
Further Reading
Age-Associated Differences in Recovery from Exercise-Induced Muscle Damage
Intermittent fasting promotes rejuvenation of immunosenescent phenotypes in aged adipose tissue
Unraveling Histone Loss in Aging and Senescence
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