Mechanisms of Ovarian Aging: A Target for Geroprotection in Women
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Yousin Suh, Ph.D.
Professor of Reproductive Sciences (in Obstetrics and Gynecology)
Professor of Genetics & Development
Columbia University, Department of Genetics and Development
Yousin Suh is the Charles and Marie Robertson professor of reproductive sciences in obstetrics and gynecology, professor of genetics and development, and director of reproductive aging at Columbia University. She investigates the (epi)genetic component that underlies the interface of intrinsic aging and disease. Her approach is based on the identification of (epi)genome sequence variants associated with age-related disease risk or its opposite, that is, an unusual resistance to such disease.
Her target populations are either cohorts of middle-aged individuals followed longitudinally for signs of all major age-related diseases or cohorts of extremely long-lived individuals who managed to ward off such diseases. To tackle the key problem of identifying the functional impact of any observed association, she applies specific functional tests, including in silico modeling, cell culture assays and mouse models. Her discoveries so far include novel, rare alleles associated with extreme longevity, sirtuin variants that confer risk of heart disease, functional noncoding variants in the gene desert chromosome 9p21 locus underlying multiple age-related diseases, longevity-associated microRNAs, and epigenetic signatures of cellular senescence.
Her contributions have been recognized with the Glenn Award for Research in Biological Mechanisms of Aging. She has organized numerous international symposiums on the functional genomics of aging, sits on the editorial boards of numerous journals including PLoS Genetics and Aging Cell as an associate editor, and is a member of advisory committees for several research institutions and companies.
Summary
The ovary is the first organ to undergo early-onset aging in the human body, with profound consequences for both fertility and overall health in women. However, the biological mechanisms driving ovarian aging remain poorly understood. To understand the molecular, cellular, and genetic basis of ovarian aging in humans, we performed integrative single-nucleus multi-omics analyses of young and reproductively aged human ovaries, uncovering coordinated changes in gene regulation across all ovarian cell types. We found that ovarian aging is marked by transcriptomic and chromatin accessibility signatures of the canonical Hallmarks of Aging. By integrating our multi-omics data with genome-wide association study (GWAS) variants linked to age at natural menopause, we demonstrate how functional genetic variants shape gene regulatory networks across ovarian cell types. Our work provides a comprehensive multimodal landscape of human ovarian aging and mechanistic insights into inherited variation influencing the timing of menopause. Our results raise the hope that geroprotectors targeting the “Hallmarks of Aging” may be used to delay ovarian aging, thereby promoting reproductive health and extending healthspan and longevity in women. Building on this research, we have initiated a clinical trial (NCT05836025) to test low-dose rapamycin, a well-known geroprotector, as an intervention strategy against aging in the ovary to explore the potential for rapamycin to delay ovarian aging and improve reproductive health.
Presentation Objectives:
- To appreciate the relationship between ovarian aging and systemic aging.
- To understand the molecular mechanisms of human ovarian aging.
- To understand the functional genetic drivers of human ovarian aging.
To appreciate the possibility that known geroprotectors may be used to delay aging in the ovary.
This page was last updated on Friday, February 28, 2025