title: Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence.
abstract: Telomeres are specialized nucleoprotein structures, which protect chromosome ends and have been implicated in the ageing process. Telomere shortening has been shown to contribute to a persistent DNA damage response (DDR) during replicative senescence, the irreversible loss of division potential of somatic cells. Similarly, persistent DDR foci can be found in stress-induced senescence, although their nature is not understood. Here we show, using immuno-fluorescent in situ hybridization and ChIP, that up to half of the DNA damage foci in stress-induced senescence are located at telomeres irrespective of telomerase activity. Moreover, live-cell imaging experiments reveal that all persistent foci are associated with telomeres. Finally, we report an age-dependent increase in frequencies of telomere-associated foci in gut and liver of mice, occurring irrespectively of telomere length. We conclude that telomeres are important targets for stress in vitro and in vivo and this has important consequences for the ageing process.
authors.affiliation: Ageing Research Laboratories, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Hewitt
authors.forename: Diana
authors.initials: D
authors.lastname: Jurk
authors.forename: Francisco D M
authors.initials: FD
authors.lastname: Marques
authors.forename: Clara
authors.initials: C
authors.lastname: Correia-Melo
authors.forename: Timothy
authors.initials: T
authors.lastname: Hardy
authors.forename: Agata
authors.initials: A
authors.lastname: Gackowska
authors.forename: Rhys
authors.initials: R
authors.lastname: Anderson
authors.forename: Morgan
authors.initials: M
authors.lastname: Taschuk
authors.forename: Jelena
authors.initials: J
authors.lastname: Mann
authors.forename: João F
authors.initials: JF
authors.lastname: Passos
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D041981:Gastrointestinal Tract / Q000166:cytology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000235:genetics; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D059506:Telomere Shortening / Q000235:genetics / Q000502:physiology*
chemical_list: D019098:Telomerase