Introduction
Welcome back to VitaDAO’s monthly longevity research newsletter!
Some species in the animal kingdom live extraordinarily long lives. They seem to be somehow protected from all the damage that we would expect to accumulate in aged tissues. Many are very large, like bowhead whales, and there is an established correlation between mass and lifespan, often attributed to slower metabolism. There are also animals like the naked mole rat, which live many times the life of a rodent of the same size with no increased risk of disease or decline of physiological function. We have a lot to learn from such species and Prof. Vera Gorbunova is doing just that - her lab focuses on understanding the underlying mechanisms of aging and how they differ between long-lived mammals and humans. We interviewed her for this month’s issue, so make sure you don’t miss this! (and if you just can’t wait, it can be found towards the bottom of this page!)
Longevity Literature Hot Picks
As so many great longevity papers are being published every month, we’ve decided to keep our newly introduced Further Reading section at the end of the newsletter! But first, here are our hotpicks of the month:
Sex- and age-dependent genetics of longevity in a heterogeneous mouse population
https://www.science.org/doi/10.1126/science.abo3191
This substantial body of work, done on the largest-ever mouse longevity study unravels the distinct genetic determinants of male vs female longevity. The group has compiled their data with other sources to produce an interactive research tool, which is quite fun to play around with: https://lisp-lms.shinyapps.io/itp-longevity-app/
Brown-fat-mediated tumour suppression by cold-altered global metabolism
https://www.nature.com/articles/s41586-022-05030-3
Cancer cells are known to utilise glycolysis to provide cellular energy - a process reliant upon glucose uptake. Non-shivering thermogenesis of adipose tissues also requires glucose uptake. Interestingly, Seki et al., show that cold exposure can lead to a non-shivering thermogenesis-induced decrease in blood glucose levels which can attenuate tumour growth!
Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions
https://www.cell.com/cell/fulltext/S0092-8674(22)01127-8
A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors
https://www.cell.com/cell/fulltext/S0092-8674(22)01173-4
For years research has implicated a role for bacteria in cancer - now two papers published in Cell provide extensive evidence that fungi are also found in numerous cancers and can even be associated with different prognoses. Certain fungi and bacteria were even found to often co-exist in some cancer types. This adds an additional level of complexity to our understanding of cancer, and could provide new markers for diagnostic and prognostic testing.
Insulin signaling in the long-lived reproductive caste of ants
https://www.science.org/doi/10.1126/science.abm8767
There is a trade-off between reproduction and lifespan in most organisms, but the queen ant is an exception. When a caste ant switches to a reproductive status of a pseudo-queen, her lifespan is extended 5x. During this switch, genes expression patters of insulin, MAPK, AKT is altered, consistent with the observed longer life.
SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction
https://onlinelibrary.wiley.com/doi/10.1111/acel.13721
Contrary to previous hypotheses that the mitochondrial SIRT3 is responsible for caloric restriction (CR) mediated lifespan extension, this study shows that deletion of SIRT3 actually extends the life of mice under CR conditions. This points to SIRT3 being dispensable for CR induced lifespan extension but it is required for aerobic capacity and oxidative metabolism.
Ketogenic diet prevents chronic sleep deprivation-induced Alzheimer’s disease by inhibiting iron dyshomeostasis and promoting repair via Sirt1/Nrf2 pathway
https://www.frontiersin.org/articles/10.3389/fnagi.2022.998292/full
An interesting interplay between sleep diet and Alzheimer’s has been described. Ketogenic diet seemed to be preventative of cognitive deficiency, amyloid deposition and hyperphosphorylated tau induced by chronic sleep deprivation by inhibiting ferroptosis and alleviating oxidative stress.
Is “cellular senescence” a misnomer?
https://link.springer.com/article/10.1007/s11357-022-00652-x
David Gems and Carina Kern argue that considering cellular senescence has been shown to play roles in healthy physiological processes such as acute wound healing and embryogenesis, perhaps the word ‘senescent’ is a misnomer as the dictionary definition implies that something is old. Instead they propose the term should be replaced with one more descriptive of the phenotype - “remodelling activation” - which would consequently replace SASP with RASP. Whilst it’s unlikely that the word will change any time soon (historically used terms have sticking power) it’s an important idea to keep in mind when thinking about what exactly a senescent cell is.
Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna
https://www.science.org/doi/10.1126/sciadv.abo5482
Another study convincingly shows how tightly connected development and aging are. Only 45 days of rapamycin treatment during early development (right after birth) were sufficient to increase lifespan by 10% in male mice. The cost of this was smaller size and slowed down development.
Drugs, clocks and exercise in ageing: hype and hope, fact and fiction
https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP282887
This review takes a broad look at the field and compares the effects of pharmacological vs non-pharmacological interventions and the accuracy and predictive power of functional measurements vs aging clocks. Roadblocks in the advancement of the field and potential future strategies are also discussed.
Aging and cancer epigenetics: Where do the paths fork?
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13709?campaign=wolearlyview
There is a clear association between aging and cancer on molecular and eidemiological level but can this also be explained via epigenetic mechanisms? While there are considerable differences between the two processes, epigenetic clocks could be key to unravel the intricacies of this relationship, especially if integrated with genetic evidence of DNA damage.
News
Celebrity Strategy Consultant Predicts What Will Be The Most Impactful Area In The Pharmaceutical Industry
Read Dr. Alex Zhavoronkov’s article on Dr. Michael Ringel’s ARDD lecture titled “The Emerging Commercial Landscape for Aging Biology-Based Therapeutics”.
The US House of Representatives held a hearing on geroscience and how it drives age-related disease and disability
https://science.house.gov/hearings/the-fountain-of-youth-the-quest-for-aging-therapies
Speakers include: Dr. Jay Olshansky, Dr. Laura Niedernhofer and Dr. Steve Horvath.
The Healthy Longevity Medicine Society Official Launch
Led by President Prof. Andrea Maier and Vice President Dr. Evelyne Bischof, the HLMS vision is “to develop longevity medicine as a respected and independent medical speciality that extends the healthspan of ageing individuals, tackles ageing mechanisms and optimizes an individual’s performance.”
Methuselah Foundation Launch the ELONgevity Protection Project
To promote human anti-aging efforts and provide members diagnosed with terminal diseases access to experimental therapies.
1st NIH SenNet Consortium meeting in Rockville
“The purpose for the Cellular Senescence Network (SenNet) is to catalyze the development of a framework for mapping cellular senescence and its associated secretory phenotype at high resolution, to provide atlases of cellular senescence in multiple tissues and under diverse conditions, including early development, and across the lifespan.”
Launch of Biotech DAO Accelerator Bio.xyz
Biotech DAO accelerator and meta-governance layer for the DeSci ecosystem! Expect resources, courses, frameworks and $100k USDC grants to enable a new generation of talented builders in DeSci to build and launch.
Hevolution Foundation Matches Funding for Impetus Grants to Accelerate Research in Neglected Areas of Healthspan Science
Upcoming conferences
2nd VitaDAO Crypto meets Longevity Symposium
October 20th, Online
Check out our 1st symposium here: https://www.youtube.com/watch?v=GJ-rJAfjhBE
VitaDAO Hackathon 2022
Ideation weekend: 28th-30th October
Hackathon weekend: 4th-6th November
Register here: https://vitadao.com/hackathon
The Longevity Summit 2022
December 7th-8th, Buck Institute for Aging, US
Funding Opportunities
The Hevolution/AFAR New Investigator Awards in Aging Biology and Geroscience Research
Providing up to 18, three-year awards of US $375,000 each and will support research projects in basic biology of aging or geroscience.
Job board
Joao Pedro de Magalhaes’ lab is looking for a researcher/developer to work on online resources for research on ageing. https://www.linkedin.com/jobs/view/3311250129/?refId=TBaRILN%2FQN6S%2FH88SMOZaA%3D%3D
Postdoc position is available at Antebi lab (molecular genetics) at the Max Planck Institute for Biology of Aging. Apply through the portal:
https://www.age.mpg.de/career-education/open-positions
Cambrian Biopharma is looking for a product manager for their biomarker development program - Project Ordo. The position could be project based, part-time or full-time.
Please contact prashant@cambrianbio.com if interested.
Gordian Bio is hiring PhDs, postdocs and technicians for two positions in San Francisco:
Molecular biologist: https://jobs.lever.co/gordian-bio/174715cc-62c5-4408-9053-51331b3f39b1
Single cell scientist: https://jobs.lever.co/gordian-bio/814a6528-4f4c-446b-9ea1-3711f1210b34
Vincere Bio is looking for 1-2 mitochondrial biologists to test mitophagy enhancers on myocardial senescence or Parkinson’s and visualise mitophagy in vivo using mouse models. Boston, MA
Contact: recruiting@vincerebio.com
DataBETA (Database for Epigenetic Evaluation for Treatment of Aging) is a non-profit, looking for a project director to hire as a contractor. More info at dataBETA.io
Reach out to Josh Mitteldorf, including why is this job best next step for your career and how will you launch the project with simultaneous fundraising: aging.advice@gmail.com
Articles/Blogs
Inside Saudi Arabia’s $20 Billion Bet On Longevity Biotechnology
Can You Increase Longevity? The Science Behind Living Longer
Hide and seek - Cancer cells hide inside each other when the immune system attacks
https://elifesciences.org/digests/80315/hide-and-seek
Original research: Transient cell-in-cell formation underlies tumor relapse and resistance to immunotherapy: https://elifesciences.org/articles/80315
DNA clocks suggest ageing is pre-programmed in our cells
Book Review
A science-based review of the world's best-selling book on aging
https://www.sciencedirect.com/science/article/pii/S0167494322002126?via%3Dihub
Podcasts
Investing in Longbio True Believers - Sebastian Brunemeier, Healthspan Capital & ImmuneAge Pharma
https://player.captivate.fm/episode/2fb68713-bea4-4706-ac3d-b19b8b53a811
Check out Sebastian Brunemeier discussing how the science of human longevity is transforming the way we treat disease.
Should Aging Be Called A Disease?
https://www.youtube.com/watch?v=9kd5mQCfIfg
Listen to longevity heavyweights Prof. Nir Barzilai and Prof. David Sinclair discussing whether aging should be classified as a disease and the associated pros and cons.
The Sheekey Science show with Prof. Charles Brenner
https://www.youtube.com/watch?v=opMijdJ6z9Q
Catch up on this interesting discussion on NAD+, aging and fertility.
Michael Levin on the Lex Fridman Podcast
https://www.youtube.com/watch?v=p3lsYlod5OU
Biology, Life, Aliens, Evolution, Embryogenesis & Xenobots.
TV Series
Limitless with Chris Hemsworth | Disney+
https://www.disneyplus.com/en-gb/movies/limitless-with-chris-hemsworth/4MIMDuD9nF2s
Trailer: https://www.youtube.com/watch?v=SJPnK_NgHVI
“Chris Hemsworth explores the different ways humans can live better for longer by taking on physical challenges such as diving in ice or climbing skyscrapers.”
Just for fun
Wordle for Genes!
https://andrewholding.github.io/gene-wordle/
Get Involved
The Norn Group: http://norn.group (responsible for the Impetus Longevity Grants) will soon be launching a program to empower people across the globe to impact the Longevity field.
https://docs.google.com/forms/d/e/1FAIpQLSdrigugaS0W5sgtbQ9l15XeOsr7OkDaNHBIKt8614ksPtxPBQ/viewform
If you train and/or employ people to work on aging, the Norn group would love to hear your ideas for what a CompBio aging course should cover.
Interview with Professor Vera Gorbunova
Prof. Vera Gorbunova is a Professor of Biology at the University of Rochester and a director of the Rochester Aging Research Center. Her research is centred around aging, cancer and genome stability. Her lab aims to understand the basic mechanisms underlying these processes by studying multiple model organisms, especially long-lived mammals.
What inspired you to enter longevity research?
This is the most fascinating problem in biology and medicine… How could I work on anything else?
Longevity research addresses a fundamental problem of biology and has relevance to every living human.
Which of the current theories of ageing do you think are the most convincing?
I find the damage accumulation theory the most convincing. However, the nature of this “damage” is a subject of debate. Most likely, this is a combination of DNA damage, mutations and epigenetic dysregulation.
How has the field changed since you started?
I witnessed tremendous progress. We now have the tools we did not have before. Genomes of various species, various other omics tools became widely available and used in everyday research. Conserved pathways of aging had been identified in model organisms.
What mistakes do you think the longevity field has made?
Too much focus on short-lived model organisms. These organisms are helpful to identify conserved aging pathways, but they are not suitable to find longevity adaptations that evolved in long-lived species.
What advice would you give to people currently working in longevity research?
Do more bold and out of the box things. We need novel approaches and new research models. When studying long-lived organisms, do not just compare young to old. Obviously, the long-lived organisms age slower. What is most important is to find the mechanisms that make them age slower.
Is ageing a disease?
From the evolutionary standpoint aging is not a disease. However, we have to approach it as a disease to develop treatments and interventions.
You have done research across the animal kingdom. How do long-lived animals benefit longevity research? What are the most promising organisms to study that are currently underexplored?
Long-lived animals are essential for longevity research as they hold the clues for long lifespan. I am particularly interested in long-lived mammals because they are phylogenetically closer to people and the discoveries would be more translatable. There are many long-lived mammals and each may have evolved unique longevity mechanisms. That is why it is important to study all of them. My group works on naked mole rats, bats, bowhead whales and many other mammalian species.
What are the most interesting insights from naked mole rat studies and what are potential ways to translate them?
There were many interesting discoveries made on naked mole rats. The most interesting ones come when researchers look at novel mechanisms not merely testing the same pathways that were shown to be important in short-lived species. Here I can name our discovery of abundant hyaluronic acid and unique ribosomal structure with split 28S rRNA that results in highly accurate protein synthesis.
Could you explain hyaluronic acid anti-tumour and pro-longevity effects you have observed, and do you see this as a potential intervention in humans?
Naked mole rat tissues are saturated with hyaluronic acid of very high molecular weight (HMW-HA). Such hyaluronic acid has antiproliferative properties and arrests proliferation of premalignant cells leading to lower cancer incidence. HMW-HA is also a potent anti-inflammatory molecule reducing inflammation in the body and through this having an anti-aging effect.
Outro
Thanks for your interest in VitaDAO's Monthly Longevity Newsletter!
We hope to keep you up to date in this rapidly expanding field. Once again, if there is anything you would like us to feature in future issues, please get in contact.
If you have been wondering what has been going on in the VitaDAO community, here are some links below to some of our highlights from the past month. We look forward to seeing you again next month!
The Longevity Decentralized Review (TLDR) by VitaDAO | With Tim Peterson
https://www.youtube.com/watch?v=MDH7ZmMgp4I
VitaDAO IP-NFT Transfer Ceremony with Molecule & ApoptoSENS
https://www.youtube.com/watch?v=nUOhVGtb3zw
Enjoyed this newsletter? Subscribing is the best way to guarantee you stay up to date with Longevity Research.
Further reading
Is early-onset cancer an emerging global epidemic? Current evidence and future implications
https://www.nature.com/articles/s41571-022-00672-8
The emerging neuroprotective roles of exerkines in Alzheimer’s disease
https://www.frontiersin.org/articles/10.3389/fnagi.2022.965190/full
Monocyte subsets display age-dependent alterations at fasting and undergo non-age-dependent changes following consumption of a meal
https://immunityageing.biomedcentral.com/articles/10.1186/s12979-022-00297-6
Reduced endosomal microautophagy activity in aging associates with enhanced exocyst-mediated protein secretion
The lysosomal proteome of senescent cells contributes to the senescence secretome
https://onlinelibrary.wiley.com/doi/10.1111/acel.13707
Psychological factors substantially contribute to biological aging:
evidence from the aging rate in Chinese older adults
https://www.aging-us.com/article/204264/text
An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory
https://www.nature.com/articles/s41556-022-00991-z
Metabolic changes in aging humans: current evidence and therapeutic strategies
https://www.jci.org/articles/view/158451
Transcriptional Heterogeneity of Cellular Senescence in Cancer
https://www.jci.org/articles/view/158451
Relationship Between 5 Epigenetic Clocks, Telomere Length, and Functional Capacity Assessed in Older Adults: Cross-Sectional and Longitudinal Analyses
https://academic.oup.com/biomedgerontology/article/77/9/1724/6473288?login=false
Dermal Tattoo Biosensors for Colorimetric Metabolite Detection
https://onlinelibrary.wiley.com/doi/10.1002/anie.201904416
Sirtuins are Not Conserved Longevity Genes
https://academic.oup.com/lifemeta/advance-article/doi/10.1093/lifemeta/loac025/6711379?login=false
Umbilical cord plasma concentrate has beneficial effects on DNA methylation GrimAge and human clinical biomarkers
https://onlinelibrary.wiley.com/doi/10.1111/acel.13696
Sexual activity and successful aging
https://link.springer.com/article/10.1007/s41999-022-00694-6
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