Project summary

The Longevity Escape Velocity Foundation (LEVF) seeks support for one of the most neglected and potentially important questions in aging research:

Can combinations of rejuvenation interventions produce dramatically greater benefits than any intervention alone?

Aging is the world’s largest cause of disease, disability, and death. More than 100,000 people die each day from age-related causes, while hundreds of millions live with frailty, dementia, cardiovascular disease, cancer, and other chronic conditions associated with biological aging.

Scientists have identified many promising interventions that target individual aspects of aging. Yet aging itself is a complex, multi-factorial process involving numerous interacting forms of biological damage.

If aging has multiple causes, it is unlikely that a single intervention will be sufficient. The greatest breakthroughs may instead come from intelligently combining interventions that act through different mechanisms.

RMR2 (Robust Mouse Rejuvenation 2) aims to help determine whether such combinations can unlock substantially greater rejuvenation effects than any individual therapy can achieve alone.

The problem

Most aging research studies one intervention at a time. Researchers test a single drug, a single genetic modification, a single cellular therapy, or a single pathway.

This approach has generated valuable insights, but it may be overlooking one of the most promising opportunities in the field.

Virtually every successful treatment for complex diseases – including HIV, cancer, tuberculosis, hypertension, and heart disease – relies on combinations of interventions rather than a single treatment.

There are strong theoretical reasons to expect the same may be true for aging.

Yet systematic combinatorial testing remains remarkably underexplored.

The opportunity

Recent advances make this an unusually timely moment to investigate rejuvenation combinations:

• Expanding libraries of promising interventions.

• Rapid progress in aging biology.

• Improved biomarkers of biological age.

• AI-assisted analysis and experimental design.

• Growing scientific evidence that multiple aging mechanisms interact.

The key question is no longer whether individual interventions can influence aging.

The key question is whether combinations can produce synergistic effects that are dramatically larger than the sum of their parts.

If the answer is yes, the implications for human health could be profound.

Why this is neglected

Current funding structures and academic incentives favour studying individual interventions.

Combinatorial research is often more complex, more expensive, harder to publish, and difficult to fit within conventional grant programmes.

As a result, a potentially high-leverage area of research receives far less attention than its importance may justify.

This is precisely the type of bottleneck where philanthropic funding can make a disproportionate difference.

What are this project's goals? How will you achieve them?

LEVF is working to accelerate progress toward rigorous testing of rejuvenation combinations through the RMR initiative.

RMR studies test whether multiple damage repair interventions, applied together in middle-aged mice, can exceed what any single intervention achieves. The target is doubling remaining lifespan from 18 months of age – a result that would be qualitatively different from the 10-25% extensions achieved by single interventions.

RMR1 is complete. The lifespan study has concluded; preliminary data support the value of combination approaches over single interventions, though more combinations need to be tested, and on a repeated basis.

RMR2 is now entering its pilot phase. The main study will test 8 interventions across approximately 2,000 mice, utilizing a design intentionally agnostic of mechanism. This is why the damage repair approach is elegant: we can "sidestep our ignorance" and minimize assumptions about how damage occurs, or how interventions achieve systemic effects, thereby minimizing risk.

There are two ways this work can create value. A dramatic result – mice living twice as long from middle age – would shift public perception that aging is malleable, catalysing funding and policy changes that accelerate the field as a whole. But even partial success – strong additive effects without full lifespan doubling – would constitute decisive evidence against the claim that aging is intractable, and would still generate information the field cannot get elsewhere: which interventions are additive, which are redundant, which damage categories are rate-limiting. This is the filtering data that tells researchers and funders which approaches are worth pursuing in humans.

Note: RMR does not assume specific interventions will translate directly from mice to humans. Different damage types may be rate-limiting in different species. What translates is the framework: the principle that addressing multiple distinct damage types produces gains that single-target approaches cannot. If true in mice, there is strong reason to believe it is true in mammals generally.

All LEVF results are published openly, making every dollar spent on RMR a contribution to the global public knowledge base on aging.

How will this funding be used?

The funding requested won't be sufficient to achieve all the above goals, but will, critically, support individual activities including:

• Prioritising candidate intervention combinations.

• Engaging leading researchers and advisors.

• Developing experimental frameworks.

• Supporting laboratory collaborations.

• Communicating findings to researchers, funders, and policymakers.

• Building the philanthropic support needed to advance the programme.

To be clear, our objective is not merely to fund another aging study. Our objective is to help establish whether combination rejuvenation therapies can substantially accelerate progress against age-related disease.

Who is on your team? What's your track record on similar projects?

LEVF occupies a unique position within longevity science. It combines Dr Aubrey de Grey’s long-standing damage-repair framework, a commitment to open science, and a singular focus on comprehensive rejuvenation rather than incremental disease-specific interventions.

The organisation combines:

• Deep engagement with the longevity research community.

• Strong connections across science, technology, and philanthropy.

• A focus on high-leverage opportunities that may otherwise remain underfunded.

• A commitment to rigorous scientific evaluation and transparent communication.

Alongside Dr Aubrey de Grey (LEVF President and Chief Science Officer), the leadership of LEVF includes David Wood, a veteran technologist from the mobile computing and smartphone industries, and Caitlin Lewis, LEVF VP of Research. Our scientific advisory board includes Maria A. Blasco (Spanish National Cancer Research Centre), Brian Kennedy (National University of Singapore), Vera Gorbunova (University of Rochester), and Marco Quarta (Phaedon Institute).

What are the most likely causes and outcomes if this project fails?

Without adequate funding, the combinatorial damage-repair initiative to comprehensively solving all age-related diseases will stall.

Note that AI itself cannot be relied on to work out in advance which treatments for aging will be most successful. AI depends on significant prior quantities of data, obtained from earlier experiments. The training of DeepMind’s AlphaFold depended on information about the 3D structure of many proteins that was painstakingly assembled by pioneering human researchers over five decades – an initiative presciently started in 1971 by Helen Berman. Again, the remarkable breakthroughs in image recognition of AlexNet in 2012, which catalysed the entire field of deep neural networks, depended on the vast ImageNet database of labelled images assembled by Stanford’s Fei Fei Li and numerous Amazon Turk contractors.

Sadly, without good progress towards positive biomedical experimental results, there's a growing risk that people will be tempted to rush AI platforms forward, with insufficient guardrails, on the assumption that advanced AI is the best way to solve aging before they (and their friends and families) succumb to aging. By hoping to solve aging, they may increase the chances of death from misaligned or misused AI.

Therefore, to the question "how to reduce the risks of existential or catastrophic outcomes from forthcoming new generations of AI", an unexpected but valid answer is "these risks can be reduced by funding some key laboratory experiments involving middle-aged mice – experiments that have a good probability of demonstrating a significant increase in the healthspan and lifespan of these mice". See the article "Removing the pressure to rush".

How much money have you raised in the last 12 months, and from where?

$630,000. This includes $110,000 from the Survival and Flourishing Fund, $300,000 and $100,000 from two donors who have requested privacy, and numerous smaller donations received via our Donations page.