title: Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks.
abstract: Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear. Here we show that gamma-H2AX foci (gamma-foci), which reveal DNA double-strand breaks (DSBs), accumulate in senescing human cell cultures and in ageing mice. They colocalize with DSB repair factors, but not significantly with telomeres. These cryptogenic gamma-foci remain after repair of radiation-induced gamma-foci, suggesting that they may represent DNA lesions with unrepairable DSBs. Thus, we conclude that accumulation of unrepairable DSBs may have a causal role in mammalian ageing.
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sedelnikova
authors.forename: Izumi
authors.initials: I
authors.lastname: Horikawa
authors.forename: Drazen B
authors.initials: DB
authors.lastname: Zimonjic
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Popescu
authors.forename: William M
authors.initials: WM
authors.lastname: Bonner
authors.forename: J Carl
authors.initials: JC
authors.lastname: Barrett
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016615:Telomere / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; C475961:gamma-H2AX protein, mouse