Longevity

Aging lies at the root of most human death and chronic disease yet its study is woefully underprioritized.

Longevity
Longevity

Senescence is the most prolific killer of the modern world. In developed nations, 90% of all deaths are caused by age-related diseases. Occurrences of dementia, heart disease, and cancer increase exponentially with age. Prior to death, old age steals away health and happiness. Loss of muscle and bone. Blindness and deafness. Cognitive decline. Depression and suicide. In the words of Philip Roth (d. 2018, congestive heart failure): “Old age isn’t a battle; old age is a massacre.”

Modern medicine continually fights against individual age-related diseases and society spends trillions of dollars on research, therapy, and care. However, the underlying mechanisms of aging are far from being fully understood. Historically, aging has been considered inevitable and outside the scope of medicine. Today, thanks to the relentless efforts of the geroscience community, these attitudes have begun to change.  

We live in a new dawn of longevity and rejuvenation science. Despite only receiving a small portion of the NIH budget, the last decade has produced numerous breakthroughs in both basic research and potential therapies. Experiments have extended the health and lifespans of mice and other model organisms dramatically, and there is reason to hope that these gains may be extended to humans in the not-so-distant future. Pragmatists see a promising new approach to unburden the healthcare system. Futurists imagine prolonging healthy lifespans beyond anything previously possible. 

Fundamental work remains.  The institutional gap that exists in-between basic research and biotech prevents efficient progress. On the academic end of the spectrum, most studies are small-scale and hypothesis driven. On the pharmaceutical and biotech industry end, drugs targeting putative aging mechanisms have recently entered development, each a big bet on one compound or another. However, the fundamentals of longevity remain underinvested in at the level of data, infrastructure and tools. The field lacks comprehensive, systematic data that will provide critical insights into the mechanisms of aging. 

The Astera Institute aims to benefit the aging-science community by promoting essential research that paints a fuller, more robust picture of the aging process and by supporting the next generation of longevity scientists.

The Rejuvenome is a Focused Research Organization established to conduct the largest and most systematic study of the biological effects of putative anti-aging interventions. The project is led by Nicholas Schaum, former Stanford postdoctoral scholar and a central coordinator of the Tabula Muris project, with an advisory board of Morgan Levine of the Yale Center for Research on Aging, Joao Pedro de Magalhaes of Liverpool’s Integrative Genomics of Ageing Group, and Tony Wyss-Coray, the D.H. Chen distinguished professor of neurology and neurological sciences at Stanford University. The Rejuvenome will coordinate with the aging science community to produce an open and comprehensive dataset describing how key biomarkers are impacted by multiple interventions across the lifespan of mice. The results will help provide a foundation for future aging research. The Rejuvenome will ultimately study the effects of a number of intervention combinations with the potential to disrupt multiple aging processes at once.

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.

Intervention Matrix

Intervention x phenotypic effect matrix under current paradigms

The Rejuvenome aims to complete the entire matrix and to use it to guide the design of combinatorial interventions.

Upon completion, The Rejuvenome will provide the most complete picture of the impact of aging interventions across multiple biomarkers. We believe this type of work is needed to more deeply grasp the nature of aging and will produce powerful new avenues for future research.

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.

We believe the Rejuvenome is a unique opportunity to unite the field in a cooperative endeavor for the advancement of aging science and betterment of human health. We will perform global analyses on critical areas that require a centralized effort not easily done within individual labs. We desire to build a community of aging researchers to design, analyze, and interpret these critical experiments. We strive to never be competitive and always cooperative.

This requires complete transparency. The internal computational team will  provide all raw and preprocessed data to the community for free. Our analyses will be reported to the community, conducted with advice from the community, and where appropriate, performed together with outside experts. Our goal is always to provide maximum benefit to everyone within the field. 

We are now hiring computational biologists and others with Rejuvenome-relevant dry-lab experience, but all motivated individuals are encouraged to apply.

Join Our Team

We are also assembling a community of external collaborators to cooperatively analyze the data and perform ancillary experiments. We are looking for external collaborators to lead analyses of the data and perform ancillary experiments in promising areas of discovery. If you have expertise in a specific organ, intervention, omic, or other related areas and desire to analyze Rejuvenome data for your own publications, we are here to help.

Reach Out To Collaborate

The Longevity Apprenticeship seeks to shape talented individuals into active contributors who can address bottlenecks in the longevity ecosystem. The program will instill good taste in aging science and give young researchers practical experience in planning and executing projects that address deficits within the field. Apprentices will work directly with Martin Borch Jensen, a former postdoctoral researcher at the Buck Institute for Research on Aging, on real projects of immediate value. 

Initial projects will include: (1) Scoping and planning a long-term project called “Measuring Causes of Age-Related Diseases (MCARD)” that aims to create a national commons of human data on causative links between the biomarkers and mechanisms of aging and specific human diseases. (2) The Relevant Animal Model Access (RAMA) program, which will synthesize current knowledge to create guidelines for which model organisms can produce results that translate to human aging in specific settings, taking into account various ageing models and different organs and areas of biology. The resulting strategic white papers should smooth the translational path for basic research in the field.

Learn More

“Can we make an immortal yeast?” The Longevity Fund founder Laura Deming wanted to know. The humble budding yeast, Saccharomyces cerevisiae, is a treasure trove of aging science. Its simple structure, easy observability, short lifespan and similarities to human genetics and aging mechanisms have made it one of the go-to screening platforms for genetic targets. If all the available knowledge was applied in a comprehensive fashion, how long could we extend the yeast lifespan? Forever? 

To answer this provocative question, The Astera Fund is supporting new work in Maitreya Dunham’s lab at The University of Washington. The lab will systematically evolve yeast, selecting directly for those that live longest. By tracking genetic change over this process, the Immortal Yeast project will identify the genes involved in yeast aging. By employing various gene knockouts, they will attempt to perform a scientific first: transform an aging organism into an immortal one.