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PROJECT SUMMARY/ABSTRACT
The world's population is aging. Since most of older people have at least one but more commonly multiple
debilitating chronic diseases, this demographic shift will result in a dramatic increase in morbidity and a burden
on our healthcare systems. This U19 proposes an integrated study to test a new approach for developing
therapies for age-related diseases. Rather than focusing on individual diseases, we explore genetic differences
between successfully aged, healthy centenarians and control individuals with no family history of extreme
longevity. Our long-term goal is to use gene variants found enriched in the centenarian genome as potential
targets for developing drugs that prevent, delay onset and progression, and possibly even revert many of the
multiple age-related diseases. The overall objective of Project 1 is to elucidate genetic variants enriched in the
centenarian genome, based on our central hypothesis that rare variants constitute an important part of the
genetic architecture of human aging and influence human lifespan on the polygenic risk background defined by
common variants. This hypothesis has been formulated on the basis of our recent whole exome sequencing
study of longevity using the Einstein centenarian cohort and will be tested by pursuing three specific aims: (I) To
identify and replicate rare variant-based longevity association; (II) To develop an integrated common variant-
based polygenic score of longevity; and (III) To study gene regulatory pathways associated with extreme human
longevity using single-cell and single-molecule analyses of centenarian blood cells. The research rationale for
Project 1 is that such variants can be functionalized by Projects 2 and 3 and used as targets for drug screening
assays to be developed by Project 4. Our proposed research will have an important positive impact: better
understanding of the genetics of extreme human longevity provided by our study of centenarian cohorts will
enable us to identify novel therapeutics that slow or mitigate aging and all associated diseases.
Status | Active |
---|---|
Effective start/end date | 8/1/23 → 7/31/24 |
Funding
- National Institute on Aging: $592,242.00
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Projects
- 1 Active
-
Genetic variant-based drug discovery targeting conserved pathways of aging
Vijg, J., Ladiges, W. C., Niedernhofer, L. J., Barzilai, N., Robbins, P. D., Suh, Y., Zhang, Z. & Robbins, P. D.
9/15/17 → 8/31/24
Project: Research project