Epigenetic regulation of senescence and aging

Florence Mahoney Lecture on Aging | Wednesday, March 12, 2014 | 3:00 to 4:00 p.m. ET

Shelley L. Berger, Ph.D.

Director, Epigenetics Program

Daniel S. Och University Professor, Department of Cell and Developmental Biology

University of Pennsylvania Perelman School of Medicine

Dr. Berger’s research focuses on the role of histone and factor post-translations modifications in chromatin regulation and of the tumor suppressor p53; Her lab investigates chromatin mechanisms and physiology during senescence and aging, gametogenesis, and underlying organismal level behavior. She has served on international committees that established nomenclature for histone modifying enzymes and help create the NIH-sponsored Human Epigenome Project.

Summary

Aging is a crucial risk factor in a constellation of human diseases, including cancer and neurodegenerative diseases. Along with other risk factors such as environmental exposures, diet, behavior, and heredity, these risks can be understood through their impact on the epigenetic landscape in ways that ultimately lead to the burden of disease. Among these risks, aging had been regarded as fixed, but current thinking holds that aging is plastic and its pace can be slowed or even reversed. Dr. Berger’s laboratory has been studying the causal roles of epigenetics in aging, and has focused on the structural features of chromatin and gene regulation in relation to senescence. These studies of the epigenetic landscape of senescent cells reveal profound alterations both in genome-wide transcription and histone post-translational modifications (which help regulate the structure of chromatin). Most of the epigenetic changes cover broad domains of the genome, and the locations and underlying gene regulatory changes indicate that, on the one hand, oncogenic escape results from induction of specific genes that regulate pluripotency, while on the other hand aging-related alterations are caused by mutations that accumulate over “open domains” in chromatin after many cell replications.. These findings provide a broad view of the relationship between aging and disease. Further, the chromatin changes lead to profound implications for potential epigenetic therapeutics to address diseases of aging.