Payel Sen, PhD

Epigenetic mechanisms contributing to loss of transcriptional fidelity during senescence and aging

Accumulation of senescent cells in aging tissues has been implicated as a primary driver of age-related functional decline. The mechanisms that contribute to the process of senescence, their build-up, and the decline of cellular health are unknown. There is growing evidence that the changes in nuclear environment and chromatin landscape contribute to these processes. We find that one consequence of these nuclear changes is aberrant transcription from within gene bodies, a process called cryptic transcription. Cryptic transcription is the creation of ribonucleic acid (RNA) from sites that are normally not exposed in healthy cells. In the proposed study, Dr. Payel Sen will dissect the mechanism upregulating cryptic transcription. The study will also examine mouse and human aged tissue samples to see if there are cryptic transcripts, possibly establishing it as a biomarker for aging. Finally, the study will inhibit formation of cryptic transcription in mice by depleting the enzymes that support its formation and examine how it impacts healthspan.