Loss of epigenetic information as a cause of mammalian aging,Cell

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Loss of epigenetic information as a cause of mammalian aging
Cell ( IF 64.5 ) Pub Date : 2023-01-12 , DOI: 10.1016/j.cell.2022.12.027
Jae-Hyun Yang ₁ , Motoshi Hayano ₂ , Patrick T Griffin ₁ , João A Amorim ₃ , Michael S Bonkowski ₁ , John K Apostolides ₄ , Elias L Salfati ₁ , Marco Blanchette ₅ , Elizabeth M Munding ₅ , Mital Bhakta ₅ , Yap Ching Chew ₆ , Wei Guo ₆ , Xiaojing Yang ₆ , Sun Maybury-Lewis ₁ , Xiao Tian ₁ , Jaime M Ross ₁ , Giuseppe Coppotelli ₁ , Margarita V Meer ₇ , Ryan Rogers-Hammond ₁ , Daniel L Vera ₁ , Yuancheng Ryan Lu ₁ , Jeffrey W Pippin ₈ , Michael L Creswell ₉ , Zhixun Dou ₁₀ , Caiyue Xu ₁₀ , Sarah J Mitchell ₁₁ , Abhirup Das ₁₂ , Brendan L O'Connell ₁₃ , Sachin Thakur ₁ , Alice E Kane ₁ , Qiao Su ₄ , Yasuaki Mohri ₁₄ , Emi K Nishimura ₁₄ , Laura Schaevitz ₁₅ , Neha Garg ₁ , Ana-Maria Balta ₁ , Meghan A Rego ₁ , Meredith Gregory-Ksander ₁₆ , Tatjana C Jakobs ₁₆ , Lei Zhong ₁₇ , Hiroko Wakimoto ₁₈ , Jihad El Andari ₁₉ , Dirk Grimm ₁₉ , Raul Mostoslavsky ₁₇ , Amy J Wagers ₂₀ , Kazuo Tsubota ₂₁ , Stephen J Bonasera ₂₂ , Carlos M Palmeira ₂₃ , Jonathan G Seidman ₁₈ , Christine E Seidman ₁₈ , Norman S Wolf ₂₄ , Jill A Kreiling ₂₅ , John M Sedivy ₂₅ , George F Murphy ₂₆ , Richard E Green ₁₃ , Benjamin A Garcia ₁₀ , Shelley L Berger ₁₀ , Philipp Oberdoerffer ₂₇ , Stuart J Shankland ₈ , Vadim N Gladyshev ₇ , Bruce R Ksander ₁₆ , Andreas R Pfenning ₄ , Luis A Rajman ₁ , David A Sinclair ₁

Affiliation

Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA; Department of Ophthalmology, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA; IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.
Cantata/Dovetail Genomics, Scotts Valley, CA, USA.
Zymo Research Corporation, Irvine, CA, USA.
Department of Medicine, Brigham and Women's Hospital, HMS, Boston, MA, USA.
Division of Nephrology, University of Washington, Seattle, WA, USA.
Division of Nephrology, University of Washington, Seattle, WA, USA; Georgetown University School of Medicine, Washington, DC, USA.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA.
Experimental Gerontology Section, NIA/NIH, Baltimore, MD, USA.
Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA; Department of Pharmacology, UNSW, Sydney, NSW, Australia.
Department of Biomolecular Engineering, UCSC, Santa Cruz, CA, USA.
Department of Stem Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Vium, San Mateo, CA, USA.
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, HMS, Boston, MA, USA.
The Massachusetts General Hospital Cancer Center, HMS, Boston, MA, USA.
Department of Genetics, HMS, Boston, MA, USA.
Department of Infectious Diseases/Virology, Section Viral Vector Technologies, Medical Faculty, University of Heidelberg, BioQuant, Heidelberg, Germany.
Paul F. Glenn Center for Biology of Aging Research, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA; Joslin Diabetes Center, Boston, MA, USA.
Department of Ophthalmology, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE, USA.
Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
Department of Pathology, University of Washington, Seattle, WA, USA.
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
Laboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD, USA.

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.

中文翻译：

表观遗传信息丢失是哺乳动物衰老的原因

所有生物都会经历熵的增加，表现为遗传和表观遗传信息的丢失。在酵母中，由于染色质修饰蛋白重新定位到 DNA 断裂，表观遗传信息会随着时间的推移而丢失，导致细胞失去其身份，这是酵母衰老的标志。使用名为“ICE”（表观基因组的诱导变化）的系统，我们发现忠实的 DNA 修复行为会在生理、认知和分子水平上促进衰老，包括表观遗传景观的侵蚀、细胞外分化、衰老和衰老。 DNA 甲基化时钟，可以通过 OSK 介导的返老还童来逆转。这些数据与衰老信息论相一致，该理论认为表观遗传信息的丢失是衰老的可逆原因。

更新日期：2023-01-12

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