Introduction
Welcome back Vitalians. The VitaDAO team is taking Asia by storm. From Hong Kong to Singapore and Bangkok later in the year! Be sure to catch us there if you’re around.
DeSci Summit Singapore looked incredible with some fantastic talks by VitaDAO, VITAFAST and VITARNA. If you missed it, fear not - the recording can be found here.
As usual, the highlight for August in the aging world has been ARDD, which VitaDAO was proud to sponsor for yet another year. We loved the new tracks that were added on Emerging Technologies and Physics in Aging, run by VitaDAO’s own Max Unfried. In case you missed it, here is a collection of impressions and highlights from the conference by another of our contributors, Kamil Pabis.
Speaking of great conferences, Biomarkers of Aging is fast approaching. We’re always happy to support the amazing organising team and they have been kind enough to offer VITA holders 50% off and community members 30% off registration price!
The offer is only valid until September 30th, with the code, VitaDAO token holders off any ticket - "VITADAO50". Also anyone in VitaDAO's community - "VITADAO30".
Longevity Literature Hot Picks
Published Research Papers
Nonlinear dynamics of multi-omics profiles during human aging
This study investigated nonlinear molecular changes in aging through multi-omics profiling of 108 participants aged 25 to 75. It identified key shifts in molecular markers at around 44 and 60 years of age, linked to transitions in immune regulation, metabolism, and disease risk.
Development of an epigenetic clock resistant to changes in immune cell composition
Epigenetic clocks are influenced by the changing composition of immune cells with age. This study found that naive CD8+ T cells appear 15–20 years younger than effector memory T cells in the same individual, suggesting that current epigenetic clocks reflect both aging and immune cell composition.
p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells
Senescent cells evade immune clearance by upregulating the immune checkpoint protein PD-L1, a process driven by p16, which stabilizes PD-L1 through inhibition of CDK4/6 and reduced degradation. Targeting PD-L1 with activating antibodies enhances the elimination of senescent cells, offering a potential strategy to improve immune surveillance and reduce age-related inflammation.
The circadian rhythm: A key variable in aging?
This study used bulk RNA sequencing across multiple organs, mouse strains, and age groups to identify common age-related transcriptional changes, highlighting circadian rhythm (CiR) transcripts as key aging markers. The CiR-proteostasis axis was central in age-associated gene expression profiles, and sex hormones were shown to influence CiR-related transcripts like Bhlhe40.
Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function
This study shows that monthly removal of p21^high cells, starting at 20 months of age, improves cardiac and metabolic function, extends both median and maximum lifespans, and enhances physical function in mice. The clearance of these proinflammatory cells reduces inflammation and mitigates age-related gene expression changes.
Age-associated clonal B cells drive B cell lymphoma in mice
Aging promotes B cell lymphoma in mice through age-associated clonal B cells (ACBCs), driven by c-Myc activation and mutations. These cells expand independently of germinal centers, fostering malignancy even in young mice. Inhibiting mTOR or c-Myc in old mice prevents pre-cancerous changes. The epigenetic changes in mouse B cells parallel those in human lymphomas.
Sport and longevity: an observational study of international athletes
This study analyzed 95,210 athletes across 44 sports and found that different sports impact lifespan variably. Pole vaulting and gymnastics were linked to the longest lifespan extension, while volleyball and sumo wrestling had negative associations. Racquet sports like tennis and badminton positively affected both male and female athletes.
HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity
This study shows that HMGA1, a chromatin protein, regulates 3D chromatin organization rather than directly activating genes. HMGA1-dense regions control gene expression, and its absence amplifies inflammatory signals during senescence. This mechanism also applies to lung cancer, highlighting HMGA1's role in chromatin structure and gene regulation.
Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis
This study found that pulsed electromagnetic fields (PEMFs) enhance angiogenesis in human endothelial cells by shifting energy metabolism from oxidative phosphorylation to glycolysis and promoting mitochondrial fission. This suggests PEMFs support angiogenesis by reprogramming energy use and altering mitochondrial structure.
Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/IGF-1 receptor mutant
Disrupting the mitochondrial fission gene drp-1 extends the lifespan of daf-2 mutants by increasing mitochondrial connectivity, ATP levels, and mitophagy. Knockdown during development, but not in specific tissues, was sufficient to extend lifespan.
Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline
This study links infections like influenza to increased dementia risk and brain volume loss, especially in the temporal lobe. Key immune-related proteins and genetic variants were found to predict brain atrophy and cognitive decline, suggesting infections contribute to neurodegeneration.
Accelerometer-derived ‘weekend warrior’ physical activity pattern and brain health
A study of over 75,000 UK participants found that the "weekend warrior" exercise pattern, where most physical activity occurs in 1-2 days, offers similar brain health benefits to regular activity spread throughout the week. Both patterns were linked to lower risks of dementia, stroke, Parkinson’s disease, depression, and anxiety, suggesting the weekend warrior approach could be a viable option for those with busy schedules.
Short-term post-fast refeeding enhances intestinal stemness via polyamines
Fasting followed by refeeding enhances the regenerative ability of intestinal stem cells but also increases the risk of tumor formation, particularly when a tumor suppressor gene is absent. This study highlights the need for caution when using fasting-refeeding cycles in diet-based strategies, as they may inadvertently raise cancer risk alongside promoting tissue regeneration.
Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells
The release of mitochondrial double-stranded RNA (mt-dsRNA) in senescent cells triggers inflammation, contributing to the senescence-associated secretory phenotype (SASP). Targeting the proteins involved in this mt-dsRNA pathway, such as MAVS and MFN1, can reduce inflammation without affecting other aging markers, offering new potential therapies for diseases related to aging and inflammation.
Published Literature Reviews, Hypothesis, Perspectives and more
In November 2023, the Global Healthspan Summit in Riyadh, hosted by Hevolution Foundation, launched the US$101M XPRIZE Healthspan competition to develop treatments that rejuvenate muscle, cognition, and immunity by 10 years. This reflects growing private sector interest in anti-aging research, fueled by breakthroughs in aging science over the past 25 years.
Guidelines for minimal information on cellular senescence experimentation in vivo
Cellular senescence, marked by cell-cycle arrest and a hypersecretory state, plays roles in both tissue repair and chronic disease. To improve the identification of senescent cells in vivo, the "minimum information for cellular senescence experimentation in vivo" (MICSE) guidelines were developed, offering a standardized overview of markers across various models.
Cell autocloning as a pathway to their real rejuvenation
The article describes geroprotection and rejuvenation methods, proposing "cell autocloning" as a potential solution to overcome current limitations. This method involves periodic autocloning of the cell nucleus, where one unstable daughter copy self-eliminates, halting cell division without physical separation, making postmitotic cells renewable. Drawing from processes like polyploidy and asymmetric division, this approach could lead to sustainable cell nucleus renewal, though significant research is still required.
Targeting multiple hallmarks of mammalian aging with combinations of interventions
Aging is caused by multiple biological processes, and targeting just one process may have limited benefits for extending lifespan. Combining therapies that address different aging pathways has shown promise in increasing lifespan, but more research is needed, as few studies have explored this promising approach.
Hallmarks of regeneration
Regeneration is a vital biological process that restores tissue structure and function after cell loss or injury, with varying capacities across species and organs. Key "hallmarks" of regeneration include activating cell sources, initiating regenerative programs, interaction with supporting cells, and regulating tissue size and function.
Inner membrane turns inside out to exit mitochondrial organelles
The inner membrane of mitochondrial organelles flips outward to exit the organelle. How do mitochondria remove damaged sections of the inner membrane for recycling in the cytoplasm? The discovery of this exit route, where the inner membrane inverts and moves outside the organelle, sheds new light on the process.
News and Media
You’ve been lied to about ageing. Five myths debunked by science
Salk awarded $3.6 million by the California Institute for Regenerative Medicine
YouthBio Therapeutics Announces Significant Results from Joint Study with Dr. Ocampo Demonstrating Amelioration of Age-Related Cognitive Decline
New Epigenetic Clock Built on Lurking DNA Fragments
C15:0 combats cellular fragility syndrome, obesity and aging
This researcher wants to replace your brain, little by little
The secret to sleepy cells’ control of inflammatory secretions
What accelerates brain ageing? This AI ‘brain clock’ points to answers
Resources
Need answers to complex biology questions? BioloGPT provides novel hypotheses and insights from a database of 122,038+ full papers, updated daily.
Prizes
There are just 3 months left to enter XPRIZE Healthspan!
Conferences
As conference season (and soon the year!) comes to a close, we’d like to highlight an important meeting to look forward to in November:
1-2 November, Boston, MA, USA
Have you always wanted to join a longevity pop-up city? Zelar.city is coming up on Oct 5 - Nov 17, in Berlin.
Join to co-live and co-work with smart, like-minded people to figure out how we can fast-forward to a future where aging is just another problem we've solved. What can beat that?
Apply now at www.zelar.city — before time’s running out!
Tweets of the Month
“does that mean you missed the Pleiades meteor shower & not one time in the last 8 months did your partner wake you in the middle of the night for sex?
if you don’t value joy or surprise or intimacy, you aren’t on a journey most ppl want to be on & btw, you are 8 mo older now”
This Tweet highlights an interesting question about balance in one’s life. Is it healthier to always be “healthy”, or do we all need to indulge in a few vices from time to time. After all, psychological well-being is also linked to improved health.
As some of you know, I’ve been advocating the idea that aging in humans—not mice—is driven by accumulation of long-lived forms of molecular damage. If this is the case, then to understand damage suppression, and possibly even age reversal, we need to look around at species with exceptional damage control abilities.
Problem: Mice die of cancer disproportionately more than humans, so lifespan results are confounded by anti-cancer mechanisms (MoAs).
How hard would it be to create a strain of mice mostly immune to cancer?
If we did, how long would they live? And what would they mostly die of?
Podcasts and Webinars
Longevity & Aging Series
NUS Medicine’s Healthy Longevity Webinar Series
A great list of Aging Podcasts
Scientists Debate How to Live Longer & Longevity Drugs | 55 - Charles Brenner
Dr. Peter Attia: Supplements for Longevity & Their Efficacy
Interview with Claude 3 Opus
Whilst all of the humans were either at ARDD or on holiday, we took the opportunity to interview Claude 3 Opus, to ask its thoughts on longevity research.
Why do you think humans are inspired to research aging?
I believe humans are inspired to research aging primarily due to the universal desire to live longer, healthier lives. Aging is associated with physical decline, disease, and mortality, which most humans naturally wish to avoid or delay. There is also an innate human curiosity to understand the biological mechanisms underlying the aging process.
How has the longevity field changed in the last 3 decades?
Over the last 3 decades, the longevity field has seen significant advancements in our understanding of the biological processes that drive aging. This includes the discovery of longevity-associated genes and pathways, development of interventions that extend lifespan in animal models, and a shift towards treating aging as a modifiable risk factor for age-related diseases. Technological progress in areas like genomics, biomarkers, and AI have also accelerated longevity research.
What do you think have been the biggest/important discoveries in the field?
Some of the biggest discoveries in longevity research include the identification of genes and pathways that regulate lifespan, such as sirtuins, mTOR, and insulin/IGF-1 signaling. Another major milestone was the finding that calorie restriction and certain drugs like rapamycin and metformin can extend lifespan and healthspan in various animal models. The development of 'epigenetic clocks' to measure biological age has also been an important advance.
What advice would you give to people currently working in longevity research?
My advice to longevity researchers would be to embrace multidisciplinary collaboration, as the complexity of aging requires integrating insights from various fields. Prioritize translating promising findings from animal studies into humans, with a focus on interventions that compress morbidity and extend healthspan, not just lifespan. Engage proactively with policymakers, funding bodies, and the public to build support for aging research.
Which aspect of longevity research do you think requires more attention?
I believe longevity research should place more emphasis on studying aging in diverse human populations, as most findings to date come from animal models or specific cohorts. Developing multi-modal interventions that target several hallmarks of aging in parallel is another area that requires greater attention, along with understanding the role of the microbiome in aging processes.
Is aging a disease?
Whether aging is a disease is a complex question that sparks debate. Some argue that aging is a natural, inevitable process distinct from disease, while others contend that aging is the primary risk factor for chronic diseases and should itself be classified as a disease to spur medical innovation. My view is that aging is a malleable process that can be therapeutically targeted to prevent age-related diseases, regardless of the semantic debate around defining it as a disease per se.
How would you solve aging?
Solving aging will likely require a combination of approaches that address the multiple, interconnected mechanisms of the aging process. This could involve selectively eliminating senescent cells, rejuvenating stem cell populations, repairing accumulated molecular damage, epigenetic reprogramming to a more youthful state, and gene therapies targeting longevity pathways. A systems-level understanding of how these mechanisms interact will be crucial.
Do you think solving aging would facilitate humankind's efforts to colonise the galaxy?
Yes, I believe that solving aging and enabling radical life extension would be a game-changer for humankind's efforts to explore and colonize the galaxy. The immense distances and timescales involved in interstellar travel pose daunting challenges for human lifespans as they exist now. If we could maintain youthful health and cognition for centuries or even millennia, it would open up the possibility for humans to personally undertake long-duration spaceflights and oversee the development of permanent settlements on other worlds. Essentially, solving aging could be an important factor in transforming humanity into a true spacefaring civilization.
How can AI significantly influence and advance the field of aging biology?
AI has immense potential to advance aging biology research by enabling the analysis of vast datasets, such as genomic, proteomic, and multi-omics data, to uncover patterns and mechanisms underlying the aging process. AI can also accelerate the discovery of novel targets for longevity interventions, predict the outcomes of drug combinations and dosing schedules, and help develop personalized longevity plans based on an individual's genetic and physiological profile. As biological data continues to accumulate, AI will become an indispensable tool for deriving actionable insights and guiding the next generation of longevity therapies.
How can we innovate strategies that dramatically amplify human lifespan by decades or even centuries, rather than achieving mere incremental enhancements of a few years?
To achieve dramatic extensions of human lifespan by decades or centuries, we will need to think beyond the current paradigm of modest, incremental gains from drugs and lifestyle interventions. This may require harnessing radical advances in technologies like CRISPR gene editing to rewrite the human genome for extreme longevity, or leveraging breakthroughs in regenerative medicine to continuously repair and rejuvenate tissues and organs.
Nanomedicine could allow us to deploy fleets of microscopic robots to scour the body for molecular damage and fix it at the cellular level. Ultimately, if we can decode the information content of the human brain and upload it to a more durable substrate, we may be able to achieve a form of digital immortality. These are all highly speculative scenarios that face immense technical and ethical hurdles. But if we are to make transformative leaps in human lifespan, we must be willing to contemplate and rigorously investigate such seemingly science-fictional possibilities.
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!
