title: SOD isoforms play no role in lifespan in ad lib or dietary restricted conditions, but mutational inactivation of SOD-1 reduces life extension by cold.
abstract: The free radical theory of aging is one of the most prominent theories of aging and senescence, but has yet to be definitively proven. If free radicals are the cause of senescence, then the cellular anti-oxidant system should play a large role in lifespan determination. Because superoxide dismutase (SOD) plays a central role in detoxifying superoxide radicals, we have examined the effects of mutational inactivation of each isoform of sod on normal lifespan and lifespan extension by dietary restriction (DR) or cold-/hypothermic-induced longevity (CHIL). We find no significant decrease in lifespan for control worms or worms undergoing DR when sod isoforms are knocked-out even though sod mutational inactivation produces hypersensitivity to paraquat. In contrast, sod-1 inactivation significantly reduces lifespan extension by CHIL, suggesting that CHIL requires a specific genetic program beyond simple reduction in metabolic rate. Furthermore, CHIL paradoxically increases lifespan while reducing resistance to oxidative stress, further disassociating oxidative stress resistance and lifespan.
authors.affiliation: Mount Sinai School of Medicine, One Gustave Levy Place, Box 1065, New York, NY 10029, USA. kelvin.yen@mssm.edu
authors.forename: Kelvin
authors.initials: K
authors.lastname: Yen
authors.forename: Harshil B
authors.initials: HB
authors.lastname: Patel
authors.forename: Alex L
authors.initials: AL
authors.lastname: Lublin
authors.forename: Charles V
authors.initials: CV
authors.lastname: Mobbs
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D016922:Cellular Senescence / Q000235:genetics; D003080:Cold Temperature; D020868:Gene Silencing; D007527:Isoenzymes; D008136:Longevity / Q000235:genetics; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010269:Paraquat / Q000633:toxicity; D013312:Stress, Physiological / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D029742:Caenorhabditis elegans Proteins; D007527:Isoenzymes; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D010269:Paraquat