title: Serum from humans on long-term calorie restriction enhances stress resistance in cell culture.
abstract: Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well.
authors.affiliation: Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO 63130, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Omodei
authors.forename: Danilo
authors.initials: D
authors.lastname: Licastro
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.forename: Seth D
authors.initials: SD
authors.lastname: Crosby
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
mesh_terms: D000375:Aging / Q000097:blood* / Q000502:physiology; D031204:Caloric Restriction; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2
chemical_list: D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D006861:Hydrogen Peroxide; D007521:Isocitrate Dehydrogenase; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000094765:Glutathione Peroxidase GPX1; D000099156:Superoxide Dismutase 2; C495635:NFE2L2 protein, human; C538784:IDH2 protein, human; C413545:glutathione S-transferase T1; C487896:GSTK1 protein, human; C000722067:GPX1 protein, human
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