Genetic variant-based drug discovery targeting conserved pathways of aging
Description: PROJECT NARRATIVE – OVERALL Aging is the most important risk factor for human chronic diseases, including type 2 diabetes, cardiovascular disease, cancer and neurodegeneration. Here we propose to continue our new approach for developing therapies for these diseases. Rather than focusing on individual diseases, we focus on the genetic differences between successfully aged, healthy centenarians and control individuals with no family history of extreme longevity. Based on results from the previous project period, many of such genetic differences involve physiological processes that have previously been shown to be involved in extreme longevity of model organisms. Using extensive genetic resources, including whole exome sequences of our ~ 700 centenarians (in the process of significant expansion), we aim to discover novel genetic variants involved in healthy aging and longevity. We will then validate these human genetic variants in other centenarian cohorts, subsequently functionalize the top candidates in vitro and in mice in vivo, and develop drug screening assays for these variants. This genes-to-drugs collaborative project is the first to use the genetics of the very rare individuals aged over a hundred in relatively good health to identify therapeutic approaches for targeting aging itself rather than its composite diseases for preventing, delaying onset and progression, and possibly even reverting many of the multiple age-related diseases.
Funder: National Institute on Aging
Funding type: cooperative_agreement
Funder scheme: U19
Start date: 2017-09-15
End date: 2028-08-31
Investigator: NIR J BARZILAI
Institution: ALBERT EINSTEIN COLLEGE OF MEDICINE
Funded outputs count: 168
Funder award ID: U19AG056278
OpenAlex ID: G9000876669