Wednesday Afternoon Lecture Series

The Annual Florence Mahoney Lecture

Aging is a crucial risk factor in a constellation of human diseases, including cancer and neurodegeneration. 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, focused on 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 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.