Whether you are a longevity neophyte or a seasoned professor, we hope this will be an interesting and valuable resource to keep you up-to-date with the most important longevity research activity happening around the globe.
Why Longevity? Humans have long desired eternal life, with reports dating as far back as the first emperor of China, Qin Shi Huang (260–210), sending hoards of people out in search of the fabled Elixir of Life. But putting dewy-eyed dreams of immortality to one side, let’s consider that for many of the leading causes of death worldwide — cancer, heart disease, neurodegeneration — the biggest underlying risk is age. A school of thought has emerged proposing that, in addition to trying to tackle these diseases individually, we should also be investing in trying to understand the mechanisms which drive ageing itself in the hope that this knowledge could allow us to tackle all of these diseases simultaneously.
Why do we think ageing can be targeted? It is clear from looking at the animal kingdom that ageing rates are not universal — with lifespan ranges from a few years in small rodents to a staggering 200 years plus for bowhead whales. Some organisms such as sea hydras are even thought to be biologically immortal. But even comparing animals with similar sizes and metabolic rates such as mice and bats we observe a 10-fold difference in lifespan, with bats able to live over 30 years. Even among humans we observe disparities of over a decade in healthspan dependent upon postcode alone! Examples such as these provide evidence that ageing is influenced both by genetics and environment.
Experimental evidence? By mutating just a single gene in the microscopic nematode C. elegans, scientists were able to extend lifespan by around 10-fold. In mammals, a 50% increase in mice lifespan has also been achieved, which if translated to humans would mean some people living beyond 160 years old. Interventions such as calorie restriction and rapamycin dosing have also been shown to extend lifespan in numerous organisms.
Treating Ageing. Hitherto, ageing is not recognised by the FDA as a disease indication that can be treated. However the trail-blazing Targeting Aging with Metformin (TAME) trial, spearheaded by Dr. Nir Barzilai, hopes to achieve just that by conducting a 6-year study following over 3000 65–79 year olds to assess whether metformin can delay the onset and progression of age-related diseases https://www.afar.org/tame-trial
If successful, this will be a landmark moment in the history of medicine, however, conducting several year long trials in elderly populations for every new intervention is unfeasible and thus it will be imperative for more robust biomarkers of ageing to be developed so efficacies of interventions can be quantified much more quickly and cheaply.
VitaDAO’s Mission. Over the past few decades biogerontology research has gained significant traction in both academia and industry, however there is still a lack of funding for early stage research projects — VitaDAO aims to bridge this “valley of death” and accelerate R&D into the extension of both human healthspan and lifespan.
This month we have seen two great projects receive approval for VitaDAO funding — with Jonathan An receiving up to 300k USD to tackle periodontitis (gum disease) with gero-science based treatments: https://snapshot.org/#/vote.vitadao.eth/proposal/0x8464713774628fa0af6262478f7c1ecccb0a3272cc72f6324183f598e9f29007 and ApoptoSENS receiving 253k USD to engineer Chimeric Antigen Receptor (CAR-NK) cells to precisely and safely eliminate senescent cells: https://snapshot.org/#/vote.vitadao.eth/proposal/0xcafd8183c8ac4990d99d90b3bd669de2c86376aa361c2384b12d578a49f686c0.
We will be keeping you up-to-date with each new project that gets funded as well as providing updates on existing projects when the data starts to roll in!
There is now such a plethora of longevity research being published on a daily basis that we would need a significant lifespan extension to read everything! So to help we have provided you with a selection of our hotpicks of the month — enjoy!
Somatic mutation rates scale with lifespan across mammals
Somatic mutations are well known to cause cancer, but they also occur in normal tissue — for example skin cells. With age these mutant but morphologically normal cells multiply but no tumour develops. This happens in multiple tissues and the number of mutant cells dramatically increases with age. The Nature study shows that mutation rates grow linearly with age across species and the calculated mutation rates per year differ significantly between species. The organism mutation rate has a strong reverse correlation to lifespan.
Don’t forget to check out our interview with Alex Cagan — the first author of this paper — below!
Multi-omic rejuvenation of human cells by maturation phase transient reprogramming
Cellular reprogramming has definitely been a hot topic in the aging field and this new paper from Reik lab shows a new method to achieve this. The novel technique outperforms other reprogramming protocols. It was demonstrated to be highly effective in rejuvenating the epigenome of human skin cells from middle aged donors and turning the clock back 30 years according to a new transcriptomic clock.
FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice
Protein restricted diets have been shown to extend lifespan in numerous organisms — here Hill et al., show that beneficial health effects of protein restriction in mice are dependent on the metabolic hormone FGF21.
Early SRC activation skews cell fate from apoptosis to senescence
Upon severe genotoxic insult, cells undergo either apoptosis or senescence — here the authors show that inhibition of the kinase SRC can cause cells to preferentially apoptose, thus highlighting a potential therapeutic avenue to target senescent cells in aged or damaged tissues.
Cell senescence, rapamycin and hyperfunction theory of aging
Prof. Mikhail Blagosklonny provides an interesting perspective that hyperfunctional signalling pathways, such as mTOR, can drive both cellular senescence and organismal ageing whilst arguing that the two are not dependent on each other.
Nutrition, longevity and disease: From molecular mechanisms to interventions
Longo and Anderson review over a century of research, adopting a multi-pillar approach, to begin formulating an optimal longevity diet:
Whilst ageing is not (yet) recognised as a disease indication, there are numerous ongoing trials aiming to tackle age-related diseases.
A team from Osaka University, led by Prof. Koshi Nishida, have announced they have successfully improved vision in near-blind patients by transplanting iPSC-derived corneal tissue.
BioAge Labs announced that the first cohort has been dosed in a Phase 1b trial of their drug BGE-105 — an inhibitor of the apelin receptor, aimed at tackling muscle atrophy.
Now that worldwide travel restrictions from the COVID-19 pandemic are easing, we can all look forward to meeting up again in person to discuss longevity research.
May 17–20, 2022, San Antonio, Texas, fully integrated hybrid (in person-virtual)
Bay Area Aging Meeting (BAAM)
20th Bay Area Aging Meeting Tuesday
May 17, 2022, UC Berkeley, Li Ka-Shing Center, Room 245
Omics Approaches and Biomarkers in Aging
Systems Aging Gordon Research Conference Systemic Processes
May 29 — June 3, 2022, Newry, ME, United States
The Reproductive Aging Conference
Jointly hosted by FASEB and the American Aging Association (AGE)
June 5–9, 2022, Palm Springs, CA
After making a seismic shake-up to the research funding process with their short application form and an astonishing turnaround of just 3 weeks from submission to decision, the Impetus Longevity Grants are back! This time the criteria are more focused, so get your thinking caps on and good luck: https://impetusgrants.org/
New Science are on a mission to create an alternative avenue for basic research to be carried out independently of academic institutions, with donors including Jaan Tallinn (co-founder of Skype) and Vitalik Buterin (creator of Ethereum) amongst others. Applications for their first 1 year fellowship closed on May 1st, but definitely worth keeping an eye on for the future. https://newscience.org/
Modulo Bio is a neuroimmunology company that harnesses the power of machine learning, patient iPSC derived cellular modeling and large scale CRISPR screening to develop therapies for neurodegenerative diseases like ALS and Frontotemporal dementia
Senior Research Associate or Research Associate
Please contact firstname.lastname@example.org for more information.
Platform developing therapeutics to extend human healthspan and lifespan
Multiple roles: https://jobs.lever.co/bioage
Early-stage stealth longevity company is hiring interns for this summer (2–3 months):
In-person / hybrid in Redwood City, CA for soon-to-be or recent graduates
Email your resume and 4–5 sentences which answer, “Why do you want to intern at our early stage biotech / longevity focused startup?” to our Recruiting Lead email@example.com. Deadline until May 31st, 2022
We are collectively funding, and advancing longevity research in an open and democratic manner. Longevity dealflow is currently looking for three positions: manager, principal and venture associate.
Newlimit are a new company hoping to tackle age-related diseases and extend lifespan by targeting epigenetic drivers of ageing. They currently have numerous roles available across a range of levels:
YC company SiPhox https://siphox.com/ is looking for someone to fill a FT or consulting d2c growth role. They are looking for someone who is interested in aging, longevity, and blood biomarkers who has marketing/startup/growth experience and can help design some branding and UX
Retro Biosciences https://retro.bio/careers/ are focusing on extending human healthy human lifespan via cellular reprogramming, autophagy & plasma-inspired therapeutics. Thy are recruiting multiple roles, the majority of which are science based.
Post-doc (assistant/associate) position in Alberto Sanz’s lab, University of Glasgow
The aim is to investigate why mitochondria produce more ROS as we age, with a view to implementing strategies to tackle mitochondrial ageing.
If you would like us to advertise any of your longevity-related positions from PhDs, to postdocs, to start-up hires etc then please get in contact and we will be glad to include them in next month’s issue.
After studying Anthropology at the University of Cambridge followed by a PhD in Evolutionary Genomics of Animal Domestication at the Max Planck institute, Dr. Cagan now works as a scientist at the Wellcome Sanger Institute — utilising the power of comparative genomics to better understand the processes of somatic evolution and how it relates to cancer and ageing. He also works as a scientific illustrator and is passionate about the combined power of art and science.
How do you think your latest paper on somatic mutations will impact the field of ageing research and what are the remaining questions?
In our paper we looked at cells in the intestinal crypt across 16 mammalian species and found a strong inverse correlation between somatic mutation rate and lifespan across. In other words the longer the lifespan of a species the slower the DNA mutation rate in the cells of that species, such that a mouse and a human end their lifespan with a similar number of somatic mutations in their intestinal cells. These findings are consistent with a role for somatic mutations in the aging process, something that has been theorized for decades. What the results don’t tell us is through what mechanisms, if any, somatic mutations are contributing to aging. This remains a fascinating open question. Our results also suggest that longer lived species than humans may have found ways to lower their mutation rate beyond our own. Studying these species and understanding how they achieve this, potentially through higher fidelity mechanisms of DNA repair, could be of great benefit.
What inspired you to enter longevity research?
Aging fascinates me because it is one of the fundamental biological processes that still remains relatively mysterious. As an evolutionary geneticist I am fascinated by exploring the relatively uncharted landscape of somatic evolution, the process by which mutations in the DNA occur and spread throughout the human body as we age. It’s long been known that this process causes cancer but due to technical limitations it has been challenging to study this process in normal tissues as we age. Now that genome sequencing methods have improved we are able to study this hitherto inaccessible process and are learning about how mutations in our cells radically alter the molecular landscape of our bodies as we age. I am excited to discover to what extent these processes may be contributing to a range of age-related diseases and potentially even aging itself.
How has the field changed since you started?
There has been an enormous surge in interest in this field since I started, both within academia as new technologies have been developed that enable us to quantify the aging process in new ways and from industry, as the potential of breakthroughs to improve the human healthspan is enormous.
Other than your own, what do you think have been the biggest/important discoveries in the field?
Because of the nature of aging as a multifactorial process there have been a multitude of important discoveries. As we have yet to fully understand which processes are the key drivers of aging it is challenging to assess their relative importance, they all contribute to our understanding. I would say that the discovery of epigenetic clocks, that telomere shortening and proteome turnover rates correlate with species lifespan and our growing understanding of cellular senescence are among the most important discoveries in the field.
What advice would you give to people currently working in longevity research?
I would say that it’s an incredibly exciting time to be working in this field and that given the multifactorial nature of aging a central challenge now is to quantify to what extent different molecular mechanisms contribute to specific phenotypic changes that occur during aging.
Which aspect of longevity research do you think requires more attention?
There are already species that have far longer lifespans than our own. More energy could be devoted to studying these species in order to understand the mechanisms by which they have extended their lifespans. In some senses evolution has already solved the problem of aging in these species and we would probably do well to try and learn from these solutions that are already sharing the planet with us.
Is ageing a disease?
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.
We are constantly striving to provide valuable content for our community, so if there is anything you would like us to feature in future issues, please get in contact.
If you are keen to see what else has been going on in the VitaDAO community, we have provided links below to some of our highlights from the past month — enjoy and we look forward to seeing you next month!
Phage Directory: How a Decentralized Network of Researchers Find Cures For Drug-resistant Infections
First VitaDAO Crypto meets Longevity Symposium
Decentralizing Science — Using Blockchain to Reinvent the Scientific Process
Novel Mechanisms to Fund Longevity Science
Heterogeneity in Senescence: from Mechanisms to Interventions with Prof Marco Demaria
How Crypto Can Help Science & Medicine by Tim Peterson