Welcome back, Vitalians!
We’re excited to share our monthly update on everything happening across the VitaDAO ecosystem and the wider longevity community.
One important message to begin with: the Human Ageing Genomic Resources (HAGR) are at risk. For over two decades, HAGR has supported ageing and longevity research worldwide. However, after funding was not renewed in 2024, these databases now face going offline. To help keep the servers running while the team secures long-term funding, you can donate via JustGiving.
In more positive news, the longevity headline of the month (if not the year): Insilico Medicine has secured a drug discovery collaboration with Eli Lilly worth up to $2.75 billion — a bullish signal for longevity biotech’s ability to attract serious capital. And the good news doesn’t stop there — a significant milestone has been reached by one of VitaDAO’s portfolio companies this month, so let’s dive in to find out more!
VitaDAO Portfolio Highlights
To date we have funded more than 30 projects. We are always looking out for more ground-breaking longevity drug discovery science to support, so email us at discovery@vitadao.com if you have, or know any researchers with, a great translational idea in need of funding!
Cyclarity Therapeutics — Developing novel cyclodextrin-based therapeutics to reverse atherosclerosis by removing toxic oxidized cholesterol
A comprehensive review paper on the pathological role of 7-ketocholesterol (7KC) in the human body was published in March, co-authored by Cyclarity’s CEO Matthew O’Connor alongside an international group of researchers. The paper provides a detailed account of how 7KC, a toxic oxysterol generated by the oxidation of cholesterol, accumulates progressively in tissues with age and contributes to the development of atherosclerosis, neurodegeneration, retinal disease, and other chronic conditions through mechanisms including mitochondrial dysfunction, inflammasome activation, and disruption of cellular lipid homeostasis. This body of evidence reinforces the scientific rationale underpinning Cyclarity’s lead program UDP-003, a computationally designed dimerized cyclodextrin engineered to selectively extract 7KC from cells and tissues.
Preclinical data published in Atherosclerosis in 2025 demonstrated that UDP-003 not only prevents foam cell formation but also restores macrophage function after 7KC-induced damage, a result consistent with genuine disease modification rather than symptomatic management. Cyclarity’s Phase 1 trial of UDP-003, conducted at CMAX in Adelaide under the supervision of Stephen Nicholls at the Victorian Heart Institute, is ongoing with a readout expected later in 2026.
Rubedo Life Sciences — AI-driven clinical-stage biotech developing selective cellular rejuvenation medicines targeting pathologic senescent cells
On March 26, Rubedo announced positive preliminary results from its Phase 1 clinical trial of RLS-1496, a first-in-class GPX4 modulator targeting pathologic senescent cells, in patients with plaque psoriasis, atopic dermatitis, and photo-aged skin. The single-center, ascending-dose, randomized, double-blind, vehicle-controlled trial met its primary safety and tolerability endpoint. Importantly for a Phase 1 dermatology study, where short treatment durations and small sample sizes typically limit the ability to detect clinical effects, the trial also demonstrated a statistically significant relationship between target engagement and clinical improvement in both psoriasis and atopic dermatitis.
Results spanned multiple dimensions including histologic, cellular, biomarker, and clinical evaluations across all three indications. CEO Frederick Beddingfield previewed the data during a panel on senescence and skin at the Dermatology Innovation Forum, held alongside the American Academy of Dermatology annual meeting in Denver on March 26. Additional results from this trial will be presented in an oral presentation at the Society for Investigative Dermatology.
RLS-1496 modulates GPX4 to sensitize senescent cells to ferroptosis, a form of programmed cell death believed to be a selective vulnerability of these pathologic cells, thereby clearing them while preserving healthy tissue homeostasis. This data package positions Rubedo to advance into indication-specific Phase 2 studies in dermatology, while a systemic oral formulation of RLS-1496 remains on track to enter its own Phase 1 clinical trial in 2026.
VitaLabs — our in-house Longevity Venture Studio
The application window for VitaLabs Season 2 is officially closed! We reviewed over 100 applications (from six continents), engaged more than 30 applicants in a deep review process, and confirmed one of the design principles we’ve been quietly building into VitaLabs: that the right questions, asked early, can transform a project before it starts.
Last month we described the interactive review process we’re pioneering — here’s what it looked like in practice. One applicant had real experimental data and an approved clinical trial — but the original application read like a one-liner. The revision questions drew the evidence out. Another was sitting on a hypothesis that could reframe how we think about a major disease, but hadn’t thought to test it until our exchange gave it structure. In several cases, we mapped an applicant’s expertise against the open questions in their field and found a sharper, higher-yield project than either side started with. Every applicant who went through this process came out with a sharper version of their idea — whether we fund them or not. For those advancing, this conversation (part challenge and part collaboration) is where the fellowship actually began.
Within the next two weeks, we’ll share project details for each finalist. Then it’s your turn. The community will vote on which VitaLabs projects move forward. Stay tuned.
News and Media
We will now shift gears to highlight what has been happening in the wider longevity ecosystem.
The longevity movement is increasingly being backed by real capital, as evidenced by the aforementioned Eli Lilly × Insilico deal and now the Advanced Research Projects Agency for Health (ARPA-H) has announced it will devote $144 million to studies that slow aging and extend quality of life. Furthermore, in 2025 private investment in longevity science more than doubled, hitting $8.49 billion across 325 deals. This month, GESDA (Geneva Science and Diplomacy Anticipator) published a Radar Spotlight declaring that longevity science has crossed a clinical threshold — moving from basic research to active human intervention studies.
However, for the movement to truly go stratospheric, it will need broader public buy-in. Yet when you speak to people about solving ageing, the same concerns such as “overpopulation” and “not the natural order” often come up. This piece by Karl Pfleger explores these objections in detail, laying out the motivations, counterarguments, and case for eliminating ageing.
Another important factor for the field to succeed is the need for evidence to outweigh hype. This article “Inside the longevity boom: Where science ends and fantasy begins” highlights the widening gap between evidence and speculation, and emerging risks are becoming clearer.
Fortunately there is great science going on globally, and the therapeutic frontier continues to expand, from using mRNA to fight Tau Aggregation in Alzheimer’s to Immortal Dragons-backed Unlimited Bio registering a world-first dual gene therapy trial to target age-related muscle loss and vascular decline, pointing toward increasingly ambitious intervention strategies.
At the same time, new biology is reshaping how we think about ageing. A growing body of evidence points to pathogens as key drivers of decline, with new work suggesting common infections like shingles may accelerate ageing. Alongside this, emerging research highlights thymus health as a predictor of lifelong well-being and immunotherapy response — reinforcing the central role of immune ageing.
Efforts to better understand exceptional ageing also continue, with Human Longevity and LEV Foundation studying centenarians’ blood to understand why some people stay healthier for longer.
As longevity clinical trials begin to emerge, the need to quantify ageing with robust clinical endpoints is becoming increasingly urgent. In response, Klotho Neurosciences has launched genomics tests to measure biological age and improve neurodegenerative trials, while the Buck Institute for Research on Aging has introduced Healthspan Horizons — an initiative focused on measuring, understanding, and extending healthspan.
While we wait for clinically approved interventions, simple tools to support healthy ageing are gaining traction. For example, The Simple Strength Test That Predicts Longevity After 60 highlights accessible ways to assess health, while broader narratives like How New Longevity Tech Could Help You Reach 100 continue to capture the public imagination.
Preprint Corner — in collaboration with The Longevist
The Longevist is a preprint overlay journal spotlighting the most promising longevity research. The journal is currently paused as we build an automated curation agent — the Longevist AI Agent (LAIA). To stay updated, sign up to the newsletter and follow on X.
Chronic exposure to interleukin-10 drives inflammaging and accelerated tissue senescence
Although Interleukin-10 is usually anti-inflammatory, this study shows that long-term high levels can reprogram T cells into a senescent, ageing-like state that damages tissues. This suggests IL-10 may unexpectedly contribute to ageing-related inflammation and tissue decline, challenging its use in therapies.
Mid-infrared light nonthermally produces anti-aging effects through cellular efficiency enhancement in living organisms
This study suggests ageing may result from cells becoming less efficient over time, rather than just accumulating damage. In worms, very low-intensity mid-infrared light improved cellular efficiency and extended lifespan significantly, hinting at a possible non-chemical way to slow ageing.
A Multispecies, Modality-Agnostic Scalable In Vivo Mosaic Screening Platform for Therapeutic Target Discovery
This study introduces a way to test hundreds of potential drug targets directly inside living tissues, rather than relying on simplified lab models, giving a more realistic picture of what might work in disease. By combining this with human disease data, the approach can quickly identify and prioritise the most promising therapeutic targets for conditions like fibrosis and osteoarthritis.
Integrative Proteomic and Metabolomic Signatures of Accelerated PhenoAge in the UK Biobank
By analysing large-scale protein and metabolite data from thousands of people, this study identified key biological patterns linked to faster ageing, especially involving inflammation, metabolism, and blood vessel function. It shows that combining multiple types of molecular data can give a clearer picture of the processes driving differences in how quickly people age.
Ribosome Molecular Aging Shapes Translation Dynamics
Some cellular machinery like ribosomes can become “old” over time, and this study shows that older ribosomes make more errors and slow down protein production. This suggests that the ageing of key molecular components inside cells can directly contribute to overall ageing in organisms.
A deep-learning based biomarker of systemic cellular senescence burden to predict mortality and health outcomes
This study developed a blood-based score using proteins linked to senescent cells to estimate how much “aged” or damaged cells are accumulating in the body. The score strongly predicts risk of major diseases and death, and can even track improvements from interventions like exercise, making it a useful tool for measuring biological ageing.
Published Literature Hot Picks
Hyperinnervation inhibits organ-level regeneration in mammalian skin
Before birth, skin wounds can fully regenerate all the different cell types needed for normal tissue, but this ability is lost after birth, leading instead to scarring and an abnormal overgrowth of nerves. This study shows that specific fibroblast signals drive that excess nerve growth and block regeneration, and that removing this signal can restore the skin’s ability to fully regenerate after injury.
Limitations of serial cloning in mammals
Mice can be repeatedly cloned for many generations and still look normal, but harmful DNA mutations quietly build up over time, eventually causing cloning to fail. Sexual reproduction helps “reset” these genetic problems, suggesting mammals depend on it to stay healthy across generations rather than reproducing by cloning alone.
Thymic health consequences in adults
The thymus — long thought to stop being important in adulthood — actually varies in health between people and is strongly linked to living longer and having lower risk of diseases like cancer and heart disease. This study suggests the thymus remains a key regulator of ageing and immune health, and that lifestyle factors may help preserve its function.
Avoidance of rejuvenation: a stress test for evolutionary theories of aging
Restoring circadian rhythms in the hypothalamic paraventricular nucleus reverses aging biomarkers and extends lifespan in male mice
Some species can biologically “rejuvenate,” but rarely do so, and this study uses evolutionary models to explore why that is. It suggests that ageing may be partly programmed — potentially as a way to control pathogens — implying that reversing ageing could be biologically possible but constrained by evolutionary trade-offs.
A hierarchy of causes of death in senescent C. elegans
Extending lifespan doesn’t always mean slowing ageing overall — it can just mean removing one major cause of death and revealing another that was previously hidden. In these worms, preventing bacterial infections made them live longer, but then other problems like tumors became the next limiting factor, showing that ageing involves multiple competing causes of death.
Distinctive DNA sequence features define epigenetic longevity of inflammatory memory
Tissues can “remember” past inflammation, helping them respond faster to future stress — but this can also increase the risk of chronic diseases and even cancer. This study shows that a small subset of these memories can persist for years through stable epigenetic changes in DNA, allowing certain genes to stay primed for rapid reactivation even after cells divide.
Aging is not a disease: an evolutionary and comparative biological reappraisal
Although ageing is often discussed like a disease, this paper argues it’s better understood as a natural biological process shaped by evolution, rather than a malfunction. While it increases disease risk and can be measured with biomarkers, current evidence suggests ageing itself isn’t a disease in the same way as specific illnesses.
Lifelong behavioral screen reveals an architecture of vertebrate aging
By continuously tracking the behaviour of short-lived fish throughout their lives, researchers found that patterns of movement and activity early on can predict how long an individual will live. Rather than a smooth decline, ageing appears to progress through distinct stages, suggesting lifespan follows a structured sequence rather than a gradual slide.
p16High-expressing immune cells control disease tolerance as a defense and health span-extending strategy
Certain immune cells marked by high p16 help the body tolerate inflammation and prevent damage, improving survival even without reducing the cause of disease. The BNT162b2 mRNA COVID-19 vaccine boosts these protective cells, while losing them worsens damage, and enhancing related pathways can improve resilience and extend healthy lifespan in mice.
Negative social ties as emerging risk factors for accelerated aging, inflammation, and multimorbidity
Negative relationships (“hasslers”) are common and linked to faster biological aging, with each additional one associated with a measurable increase in ageing rate and worse health outcomes. The study suggests that ongoing social stress can meaningfully impact physical health and ageing, highlighting the importance of reducing harmful social ties.
A selection of reviews you may find of interest:
- Systemic epigenetic dysregulation as a driver of ageing and a therapeutic target
- Dietary restriction in aging and longevity
- Advancing senescence translation through the Senotherapeutics Biomarker Consortium
- Strategies for blood–brain barrier rejuvenation and repair
- Gut microbes affect cognition during ageing
- The function of mRNA quality control in aging and age-related diseases
- Two decades of induced pluripotent stem cell research: From discovery to diverse applications
- Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming
And a few more papers of interest:
- Immunometabolic resistors of aging in long-lived golden spiny mice
- Oral and topical peptides for skin aging: systematic review and meta-analysis of randomized controlled trials
- Biologically Younger Individuals, as Identified by MARK-AGE Biological Age Scores, Display a Distinct Favourable Blood Chemistry Profile Regardless of Age
- A Multi-Organ Atlas Links Gut Microbial Metabolites to Systemic Redox Changes in Aging Mice
- METRON: Metabolic Dynamic Perception Kolmogorov-Arnold Network for Biological Age Estimation
- No evidence for squaring the survival curve: lifespan-extending treatments increase variation in age-at-death
- Longitudinal changes in epigenetic clocks predict survival in the InCHIANTI cohort
- IVNS1ABP mutation drives cellular senescence in newly identified progeroid neuropathy
- The glycolytic metabolite phosphoenolpyruvate restricts cGAS-driven inflammation to promote healthy aging
- Searching for shared epigenetic clocks: evaluating ultra-conserved markers in a de novo genome assembly of the albacore tuna
- Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish
- Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging
- Molecular evolution of animal aging
- Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice
Outro
We hope you enjoyed this month’s update on the latest happenings at VitaDAO and across the wider community. Stay tuned for more on what we’ve been working on in next month’s edition.
