title: Comparative levels of DNA breaks and sensitivity to oxidative stress in aged and senescent human fibroblasts: a distinctive pattern for centenarians.
abstract: Basal and H(2)O(2)-induced DNA breaks as well as DNA repair activity and efficacy of the antioxygenic system were determined in human dermal fibroblasts explanted from either (i) young donors and passaged serially to reach replicative senescence or (ii) young, old and centenarian donors and shortly propagated in culture. These fibroblasts have been employed as an in vitro and ex vivo model, respectively, to evaluate comparatively DNA integrity during senescence (increasing population doubling levels) and aging (increasing donor age). Constitutive levels of DNA total strand breaks, as determined by the alkaline extraction procedure, changed moderately among the different cell lines, which exhibited, however, significant differences in the amount of either single or double strand breaks. The former decreased along with both aging and senescence; the latter augmented during senescence while being virtually steady during aging. Moreover, fibroblasts from centenarians showed to be less sensitive to H(2)O(2)-induced DNA damage than other ex vivo fibroblasts. This feature could not account for either increased DNA repair activity or higher efficacy of the antioxygenic system and pointed, instead, to an intrinsic nuclear stability which might be typical of centenarian fibroblasts and potentially functional to longevity.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni 50, 50134 Florence, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Chevanne
authors.forename: Riccardo
authors.initials: R
authors.lastname: Caldini
authors.forename: Donatella
authors.initials: D
authors.lastname: Tombaccini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mocali
authors.forename: Guido
authors.initials: G
authors.lastname: Gori
authors.forename: Francesco
authors.initials: F
authors.lastname: Paoletti
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D016922:Cellular Senescence; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide