ArticleCell2023
Loss of epigenetic information as a cause of mammalian aging.
Erratum issuedOpen access · greenAbstract read
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Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 375 papers.
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375citing papers in PubMed
92.5field-weighted citation impact, top 1% of its field
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Who cites it
375 citing papers in PubMed, 577 citations in OpenAlex.
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315 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
64 authors at 17 institutions in 5 countries.
Jae-Hyun YangPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA. Electronic address: jae-hyun_yang@hms.harvard.edu.
Motoshi HayanoPaul 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.
Patrick T GriffinPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
João A AmorimPaul 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.
Michael S BonkowskiPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
John K ApostolidesComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.
Elias L SalfatiPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Marco BlanchetteCantata/Dovetail Genomics, Scotts Valley, CA, USA.
Elizabeth M MundingCantata/Dovetail Genomics, Scotts Valley, CA, USA.
Mital BhaktaCantata/Dovetail Genomics, Scotts Valley, CA, USA.
Yap Ching ChewZymo Research Corporation, Irvine, CA, USA.
Wei GuoZymo Research Corporation, Irvine, CA, USA.
Xiaojing YangZymo Research Corporation, Irvine, CA, USA.
Sun Maybury-LewisPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Xiao TianPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Jaime M RossPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Giuseppe CoppotelliPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Margarita V MeerDepartment of Medicine, Brigham and Women's Hospital, HMS, Boston, MA, USA.
Ryan Rogers-HammondPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Daniel L VeraPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Yuancheng Ryan LuPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Jeffrey W PippinDivision of Nephrology, University of Washington, Seattle, WA, USA.
Michael L CreswellDivision of Nephrology, University of Washington, Seattle, WA, USA; Georgetown University School of Medicine, Washington, DC, USA.
Zhixun DouDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA.
Caiyue XuDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA.
Sarah J MitchellExperimental Gerontology Section, NIA/NIH, Baltimore, MD, USA.
Abhirup DasPaul 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.
Brendan L O'ConnellDepartment of Biomolecular Engineering, UCSC, Santa Cruz, CA, USA.
Sachin ThakurPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Alice E KanePaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Qiao SuComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.
Yasuaki MohriDepartment of Stem Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Emi K NishimuraDepartment of Stem Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Laura SchaevitzVium, San Mateo, CA, USA.
Neha GargPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Ana-Maria BaltaPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Meghan A RegoPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
Meredith Gregory-KsanderSchepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, HMS, Boston, MA, USA.
Tatjana C JakobsSchepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, HMS, Boston, MA, USA.
Lei ZhongThe Massachusetts General Hospital Cancer Center, HMS, Boston, MA, USA.
Hiroko WakimotoDepartment of Genetics, HMS, Boston, MA, USA.
Jihad El AndariDepartment of Infectious Diseases/Virology, Section Viral Vector Technologies, Medical Faculty, University of Heidelberg, BioQuant, Heidelberg, Germany.
Dirk GrimmDepartment of Infectious Diseases/Virology, Section Viral Vector Technologies, Medical Faculty, University of Heidelberg, BioQuant, Heidelberg, Germany.
Raul MostoslavskyThe Massachusetts General Hospital Cancer Center, HMS, Boston, MA, USA.
Amy J WagersPaul 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.
Kazuo TsubotaDepartment of Ophthalmology, Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Stephen J BonaseraDivision of Geriatrics, University of Nebraska Medical Center, Durham Research Center II, Omaha, NE, USA.
Carlos M PalmeiraDepartment of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
Jonathan G SeidmanDepartment of Genetics, HMS, Boston, MA, USA.
Christine E SeidmanDepartment of Genetics, HMS, Boston, MA, USA.
Norman S WolfDepartment of Pathology, University of Washington, Seattle, WA, USA.
Jill A KreilingDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
John M SedivyDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
George F MurphyDepartment of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
Richard E GreenDepartment of Biomolecular Engineering, UCSC, Santa Cruz, CA, USA.
Benjamin A GarciaDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA.
Shelley L BergerDepartment of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA.
Philipp OberdoerfferLaboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD, USA.
Stuart J ShanklandDivision of Nephrology, University of Washington, Seattle, WA, USA.
Vadim N GladyshevDepartment of Medicine, Brigham and Women's Hospital, HMS, Boston, MA, USA.
Bruce R KsanderSchepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, HMS, Boston, MA, USA.
Andreas R PfenningComputational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA.
Luis A RajmanPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA.
David A SinclairPaul F. Glenn Center for Biology of Aging Research, Department of Genetics, Blavatnik Institute, Harvard Medical School (HMS), Boston, MA, USA. Electronic address: david_sinclair@hms.harvard.edu.
Harvard University · USUniversity of Pennsylvania · USBrigham and Women's Hospital · USCarnegie Mellon University · USDovetail Genomics (United States) · USMassachusetts Eye and Ear Infirmary · USUniversity of Washington · USBrown University · USHeidelberg University · DEMassachusetts General Hospital · USTokyo Medical and Dental University · JPUniversity of California, Santa Cruz · USGeorgetown University · USJoslin Diabetes Center · USKeio University · JPUniversity of Coimbra · PTUniversity of Nebraska Medical Center · US
Funding
Somatic Activation of Retrotransposition: A New Molecular Mechanism of Aging?P01AG051449 · NIA · BROWN UNIVERSITY · PI John M Sedivy · 2016 to 2026
$30.4MSTRUCTURAL BASIS FOR EPIGENETICS IN AGING AND LONGEVITYP01AG031862 · NIA · WISTAR INSTITUTE · PI SCHULTZ, DAVID C · 2008 to 2022
$28.3MVISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5MTraining Program in Molecular and Integrative Physiological SciencesT32HL007118 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI LU, QUAN · 1985 to 2025
$14.3MTranslational Researchin Aging Trainnig ProgramT32AG023480 · NIA · HEBREW REHABILITATION CENTER FOR AGED · PI LIPSITZ, LEWIS · 2004 to 2024
$7.6MCell Biology of Astrocytes in the Optic Nerve HeadR01EY019703 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Tatjana Claudia Jakobs · 2009 to 2026
$6.2MMECHANISMS OF REPLICATIVE SENESCENCE IN CELLSR01AG016694 · NIA · BROWN UNIVERSITY · PI SEDIVY, JOHN M · 1999 to 2024
$5.7MRole of Sgs1 DNA helicase in telomere maintenanceR01AG019719 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SINCLAIR, DAVID A. · 2001 to 2022
$5.3MJuxta-glomerular cells serve as glomerular epithelial cell progenitors in glomerular diseaseR01DK097598 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES, WESSELY, OLIVER · 2014 to 2022
$5.2MQUANTITATIVE ASSESSMENT OF BIOLOGICAL AGE AND ITS APPLICATIONSR01AG065403 · NIA · YALE UNIVERSITY · PI Vadim N. Gladyshev, Albert Tzongyang Higgins-Chen · 2020 to 2026
$4.2MSIRT1 as a regulator of health and lifespan of mammalsR37AG028730 · NIA · HARVARD MEDICAL SCHOOL · PI SINCLAIR, DAVID A. · 2012 to 2021
$4.1MCELL CYCLE PROTEINS AND GLOMERULAR APOPTOSISR01DK056799 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES · 2000 to 2014
$3.6MNEI NIH HHS P30 EY003790NEI NIH HHS R01 EY019703NHLBI NIH HHS T32 HL007118NIA NIH HHS F99 AG073499NIA NIH HHS K99 AG055683NIA NIH HHS K99 AG068303NIA NIH HHS K99 AG070102NIA NIH HHS P01 AG031862NIA NIH HHS P01 AG051449NIA NIH HHS R00 AG055683NIA NIH HHS R00 AG070102NIA NIH HHS R01 AG016694NIA NIH HHS R01 AG019719NIA NIH HHS R01 AG028730NIA NIH HHS R01 AG064223NIA NIH HHS R01 AG065403NIA NIH HHS R37 AG028730NIA NIH HHS T32 AG023480NIDDK NIH HHS R01 DK056799NIDDK NIH HHS R01 DK097598
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.
Indexed as
AgingEpigenesis, GeneticAnimalsDNA MethylationEpigenomeMammalsNucleoproteinsSaccharomyces cerevisiaeNucleoproteinsagingchromatinDNA damageepigenetic clockepigenetic reprogrammingRCMrelocalization of chromatin modifiersenescence
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