Abstract

Abstract Epigenetic alterations are one of the key hallmarks of aging. How epigenetic changes broadly affect euchromatin-heterochromatin balance, three-dimensional chromatin conformation, histone composition and global transcriptome in aging have been limitedly addressed. These outstanding questions are key to understanding the susceptibility of aged tissue to develop cancers, the incidence of which exponentially increases with age. Using murine liver as a model organ and an integrated multi-omics approach, we find that aged cells assume a repressed chromatin state characterized by condensed chromatin, broad heterochromatinization, and global suppression of the transcriptome. At the local level, there are site-specific chromatin openings with simultaneous derepression of genes. Our findings reveal a unique chromatin state in aging with opposing changes at the global and local levels. Citation Format: Payel Sen. Epigenetics mechanisms of tissue aging [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA016.

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