title: Key proteins and pathways that regulate lifespan.
abstract: Here, we review three sets of key proteins and their corresponding downstream pathways that have been linked to extending lifespan and promoting health span in a wide range of organisms. In particular, we review the biology of the sirtuin family of proteins, the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway, and the mechanistic target of rapamycin (mTOR). Using insights derived from simple model organisms, mice, and humans we discuss how these proteins and pathways may potentially alter the rate of aging. We further describe how knowledge of these pathways may lead to the rational design of small molecules that modulate aging and hence alter the propensity for a host of age-related diseases.
authors.affiliation: From the Center for Molecular Medicine, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Haihui
authors.initials: H
authors.lastname: Pan
authors.affiliation: From the Center for Molecular Medicine, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 finkelt@nih.gov.
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans; D031204:Caloric Restriction; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008136:Longevity; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction; D037761:Sirtuins / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D037761:Sirtuins
keywords: IGF-1; aging; insulin-like growth factor (IGF); lifespan; mammalian target of rapamycin (mTOR); mouse genetics; sirtuin; sirtuins