title: Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and aging phenotypes in the skin.
abstract: Cellular senescence arrests the proliferation of mammalian cells at risk for neoplastic transformation, and is also associated with aging. However, the factors that cause cellular senescence during aging are unclear. Excessive reactive oxygen species (ROS) have been shown to cause cellular senescence in culture, and accumulated molecular damage due to mitochondrial ROS has long been thought to drive aging phenotypesin vivo. Here, we test the hypothesis that mitochondrial oxidative stress can promote cellular senescence in vivo and contribute to aging phenotypes in vivo, specifically in the skin. We show that the number of senescent cells, as well as impaired mitochondrial (complex II) activity increase in naturally aged mouse skin. Using a mouse model of genetic Sod2 deficiency, we show that failure to express this important mitochondrial anti-oxidant enzyme also impairs mitochondrial complex II activity, causes nuclear DNA damage, and induces cellular senescence but not apoptosis in the epidermis. Sod2 deficiency also reduced the number of cells and thickness of the epidermis, while increasing terminal differentiation. Our results support the idea that mitochondrial oxidative stress and cellular senescence contribute to aging skin phenotypes in vivo.
authors.affiliation: Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Velarde
authors.forename: James M
authors.initials: JM
authors.lastname: Flynn
authors.forename: Nicholas U
authors.initials: NU
authors.lastname: Day
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D016922:Cellular Senescence; D004249:DNA Damage; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010641:Phenotype; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2