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Aging_Primates - BREVIA Cellular Senescence in Aging...

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Cellular Senescence in Aging Primates Utz Herbig, 1 Mark Ferreira, 1 Laura Condel, 2 Dee Carey, 2 John M. Sedivy 1 * T he aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as repli- cative senescence. Whether cellular senescence contributes to organismal aging has been con- troversial. To reinvestigate this question, we assayed the skin of aging baboons for telo- mere dysfunction, a recently discovered bio- marker of cellular senescence ( 1 ). Like humans, baboons have a relatively long life span and show age-dependent telo- mere shortening ( 2 ). Baboon skin fibroblasts undergo replicative senescence upon serial pas- sage in culture, with characteristics identical to those of human fibroblasts. Senescent baboon fibroblasts display DNA damage foci that con- tain phosphorylated histone H2AX ( g -H2AX), activated ataxia-telangiectasia mutated (ATM) kinase ATM(Ser 1981 ), and p53 binding protein (53BP1), and they express activated p53(Ser 15 ) and elevated levels of p21 CIP1 . More than 80% of senescent baboon fibroblasts in vitro display telomere dysfunction–induced foci (TIFs), as determined by the colocalization of g -H2AX with telomeres. Full-thickness skin biopsies were obtained from 30 baboons (15 male and 15 female), rang- ing in age from 5 to 30 years, that were born and raised at the Southwest Regional Primate Center under controlled conditions. The tissue was har- vested from the medial aspect of the forearm, a surface that is relatively protected from radiation and injury. The number of dermal fibroblast nu-
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