The Rejuvenome Project Seeks to Carry Out Combined Longevity Intervention Studies in Mice

The Rejuvenome project at the Astera Institute aims to fill an important gap in research and development aimed at the slowing or reversing mechanisms of aging. Very little work in academia or industry assesses the outcome of combined treatments. Are several different senolytic drugs targeting difference mechanisms of senescent cell death, at lower doses, much better than just one senolytic drug, at a higher dose, at clearing harmful senescent cells from old tissues? Do aged mice live longer in good health with senolytics to remove senescent cells plus flagellin immunization to improve the gut microbiome plus exosome therapy to spur greater regeneration of tissues? Does in vivo reprogramming to reset epigenetic marks in aged cells plus CDC42 inhibition to enhance hematopoiesis produce greater extension of life in mice than either alone?

Projects such as these could have been conducted a hundred times over, in dozens of ways, over the past decade. Yet they have not been. Intellectual property and perverse regulatory incentives make it hard enough to proceed to ensure that few groups pursue this path. Yet combining approaches to the treatment of aging is absolutely vital in order to achieve meaningful results. Aging is caused, at root, by a set of distinct processes, the creation of quite different forms of cell and tissue damage that arise out of the normal operation of healthy metabolism. Any one therapy can address only one of these processes, leaving the rest of aging to progress unaffected. The gains will be only incremental. The research and development communities are failing us in their neglect of this point.

Thus philanthropic funding must step in to conduct this sort of research, and that is what the Astera Institute principals intend. Rejuvenome plans to run large, robust mouse studies in aged mice. Some of their studies are planned to combine interventions known to or suspected to extend life in mice, in order to determine synergies. The work is expected to launch in earnest, once the mouse study population is old enough, in 2022. Rejuvenome expects to accept solicitations from the community in the near future as to the best combinations of interventions to assess in this fashion.


A key current limitation in the longevity field is that deep biological studies on individual interventions have primarily been investigated independently and in an ad hoc fashion, leading to a lack of comprehensive data on any one intervention. One project examines brain aging but doesn't measure lifespan, while another measures metabolism but doesn't track epigenetics, and yet another looks just at lifespan itself. This fractured approach makes it difficult to compare or combine aging interventions within a common framework.

To resolve this problem, the Rejuvenome will conduct a large-scale experiment in genetically diverse mice to measure system-wide multi-omics spanning a panel of rejuvenation interventions. By measuring multiple hallmarks of aging across the lifespan of mice, the project will provide a high-resolution description of the interconnection or independence of different aspects of the aging process and of how interventions alter these pathways. The resulting intervention-effect matrix will support the field in its advance towards better interventions.

Ultimately, the Rejuvenome will test combinations of interventions designed to target multiple aspects of aging simultaneously. There is good reason to believe such combinations will produce synergistic effects. Multiple gene knockouts in C. elegans have been shown to increase lifespan by 10x, and a combination of three compounds extended lifespan in flies beyond the effects of any of the individual components - a similar multifaceted approach could produce the longest living mice and suggest potential future multi-factorial therapies for humans.

Astera Institute

The Astera Institute was created to bring humanity the greatest imaginable good in the most efficient possible way. When your ambitions are boundless, but your resources are finite, leverage is your friend. In the words of Konrad Zuse, "I was too lazy to calculate, so I invented the computer." Inspired by such extreme examples of "work smarter," Astera seeks to activate the areas of exponential latent potential within science and technology. We want to create benevolent super-intelligence, live to 200, fix science, and do engineering worthy of Asimov. Astera Institute was established by Jed McCaleb. It is a 501c3 non-profit dedicated to developing high leverage technologies that can lead to massive returns for humanity. Astera's unusually high impact derives from housing moonshots and novel scientific research that have no other natural home in today's research and development landscape. Astera focuses on longevity, AGI, metascience, and frontier engineering.

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