$AUBRAI: The first AI Agent for Longevity Research

The aim of the RMR project pipeline is an ambitious one: to identify a longevity intervention or treatment program which doubles the remaining lifespan of wild-type adult mice. While the landscape of longevity interventions continues to balloon, nearly all therapies zero in on taking a very similar approach, tackling one specific hallmark of aging, ignoring all others. At LEV Foundation, we believe robust rejuvenation will require targeting multiple aging hallmarks simultaneously. Importantly now is the time to begin this approach, a strategy largely underemployed by the research and startup communities.

While the RMR2 program aims to achieve robust rejuvenation in rodents, the implications of a successful outcome reach far beyond laboratory animals. Demonstrable rejuvenation in aged wild-type animals is a key step in securing broad public support of rejuvenation medicine extending beyond ‘soft’ targets such as lifestyle and supplementation.

Patients:

The target patients are individuals experiencing age-related diseases and degenerative conditions resulting from the biological aging process. This includes those suffering from Alzheimer's disease, cardiovascular issues, osteoarthritis, and a general decline in physiological functions affecting quality of life.

Current Treatment Methods:

Presently, medical interventions focus on managing symptoms rather than addressing the root causes of aging. Treatments are typically disease-specific, aiming to slow progression or alleviate symptoms without reversing the underlying cellular and molecular damage that accumulates with age. There is no comprehensive therapy that targets the fundamental mechanisms of aging.

Objective:

To double the average remaining lifespan of normal, middle-aged mice. Putting that in numbers: normal mice live about 2.5 years, so this study wants to get them to 3.5 years with treatments that begin when they are 1.5 years old.

Significance:

Thus far, the best life extension that mouse researchers have ever achieved when starting at 18 months is about four months, so that's only 1/3 of what we're shooting for. That's bad enough—but what's far worse is that we could already get those four months half a century ago! It's exactly like protein folding: decades of attempts to predict proteins' 3D shapes from their amino acid sequences, negligible progress (at least by the CASP competition's metric), then bang. So this will, truly, be aging's AlphaFold moment—and far more, because it will reverberate across the whole of humanity, not just the research community.

It will give politically sensitive researchers "permission" to say enormously more optimistic things than now about the timeframe for reaching longevity escape velocity (in humans). That will mobilize the world's foremost talk show hosts, podcasters, and YouTubers—and that, in turn, will instantly initiate a bona fide War On Aging. Finally, society will treat aging the way it should have always treated it: as our mightiest enemy, but one that we can now vanquish.

Briefly, this falls into two subcategories: (1) analysis of the non-invasive data we have collected on the health of the mice, such as how they look, what they weigh, their memory, hearing, eyesight, strength, endurance etc. This is ongoing, but we can't form firm conclusions until the study is complete, which will be another couple of months. The other subcategory is (2) biochemical and genetic analysis of the organs we've stored from the mice; that's a lot of work (and money) and we have deprioritised it while we secured some expert collaborators for the various assays. The cost of these analyses will be around $1M in total - but they are not the main priority right now.

The top-line summary is that we have conclusively validated the core concept of this study design, namely that combining damage-repair interventions starting in middle age indeed gives a greater postponement of sickness and death than any one on its own. Our eventual goal is to get a much greater amount of postponement than the four months or so that can be achieved with calorie restriction (begun in middle age, which is what we're doing); no one has ever done that with any intervention. In this first study we have just about equalled that effect size, but we haven't significantly beaten it; we are sure that this is simply because we didn't use a broad enough portfolio of interventions, such that some of the types of damage that kill mice were not being addressed by any of our treatments.

Initial funds of $200,000 will be used to support the first round of pilot studies outlined in Milestone 1. The total project is outlined, describing milestones 1-3. Upon successful completion of the first milestone, additional funding will be used to for milestones 2 and 3 according to the description below.