한빛사논문
- 조회2,287
Jae-Hyun Yang1,29, Motoshi Hayano1,2,29, Patrick T. Griffin1, João A. Amorim1,3, Michael S. Bonkowski1, John K. Apostolides4, Elias L. Salfati1,2,8, Marco Blanchette5, Elizabeth M. Munding5, Mital Bhakta5, Yap Ching Chew6, Wei Guo6, Xiaojing Yang6, Sun Maybury-Lewis1, Xiao Tian1, Jaime M. Ross1, Giuseppe Coppotelli1, Margarita V. Meer7, Ryan Rogers-Hammond1, Daniel L.Vera1, Yuancheng Ryan Lu1, Jeffrey W. Pippin8, Michael L. Creswell8,9, Zhixun Dou10, Caiyue Xu10, Sarah J. Mitchell11, Abhirup Das1,12, Brendan L. O’Connell13, Sachin Thakur1, Alice E. Kane1, Qiao Su4, Yasuaki Mohri14, Emi K. Nishimura14, Laura Schaevitz15, Neha Garg1, Ana-Maria Balta1, Meghan A. Rego1, Meredith Gregory-Ksander16, Tatjana C. Jakobs16, Lei Zhong17, Hiroko Wakimoto18, Jihad El Andari19, Dirk Grimm19, Raul Mostoslavsky17, Amy J. Wagers20,27, Kazuo Tsubota2, Stephen J. Bonasera21, Carlos M. Palmeira22, Jonathan G. Seidman18, Christine E. Seidman18, Norman S. Wolf23, Jill A. Kreiling24, John M. Sedivy24, George F. Murphy25, Richard E. Green13, Benjamin A. Garcia10, Shelley L. Berger10, Philipp Oberdoerffer26, Stuart J. Shankland8, Vadim N. Gladyshev7, Bruce R. Ksander16, Andreas R. Pfenning4, Luis A. Rajman1, David A. Sinclair1,30
1Paul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA
2Department of Ophthalmology, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
3IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal
4Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA
5Cantata/Dovetail Genomics, Scotts Valley, CA, USA
6Zymo Research Corporation, Irvine, CA, USA
7Department of Medicine, Brigham and Women’s Hospital, HMS, Boston, MA, USA
8Division of Nephrology, University of Washington, Seattle, WA, USA
9Georgetown University School of Medicine, Washington, DC, USA
10Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA
11Experimental Gerontology Section, NIA/NIH, Baltimore, MD, USA
12Department of Pharmacology, UNSW, Sydney, NSW, Australia
13Department of Biomolecular Engineering, UCSC, Santa Cruz, CA, USA
14Department of Stem Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan
15Vium, San Mateo, CA, USA
16Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, HMS, Boston, MA, USA
17The Massachusetts General Hospital Cancer Center, HMS, Boston, MA, USA
18Department of Genetics, HMS, Boston, MA, USA
19Department of Infectious Diseases/Virology, Section Viral Vector Technologies, Medical Faculty, University of Heidelberg, BioQuant, Heidelberg, Germany
20Paul F. Glenn Center for Biology of Aging Research, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
21Division of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE, USA
22Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal
23Department of Pathology, University of Washington, Seattle, WA, USA
24Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA
25Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA
26Laboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD, USA
27Joslin Diabetes Center, Boston, MA, USA
28Present address: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA
29These authors contributed equally.
30Lead contact
Corresponding authors: Jae-Hyun Yang, David A. Sinclair
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.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-02-16)
- 국외 연구진
- 생명과학 > 노화/암생물학
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