Loss of epigenetic information as a cause of mammalian aging

Citation:

Yang J-H, Hayano M, Griffin PT, Amorim JA, Bonkowski MS, Apostolides JK, Salfati EL, Blanchette M, Munding EM, Bhakta M, Chew YC, Guo W, Yang X, Maybury-Lewis S, Tian X, Ross JM, Coppotelli G, Meer MV, Rogers-Hammond R, Vera DL, Lu YR, Pippin JW, Creswell ML, Dou Z, Xu C, Mitchell SJ, Das A, O'Connell BL, Thakur S, Kane AE, Su Q, Mohri Y, Nishimura EK, Schaevitz L, Garg N, Balta A-M, Rego MA, Gregory-Ksander M, Jakobs TC, Zhong L, Wakimoto H, El Andari J, Grimm D, Mostoslavsky R, Wagers AJ, Tsubota K, Bonasera SJ, Palmeira CM, Seidman JG, Seidman CE, Wolf NS, Kreiling JA, Sedivy JM, Murphy GF, Green RE, Garcia BA, Berger SL, Oberdoerffer P, Shankland SJ, Gladyshev VN, Ksander BR, Pfenning AR, Rajman LA, Sinclair DA. Loss of epigenetic information as a cause of mammalian aging. Cell 2023;186(2):305-326.e27.

Date Published:

2023 Jan 19

Abstract:

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.

Last updated on 01/31/2023