title: The impact energy metabolism and genome maintenance have on longevity and senescence: lessons from yeast to mammals.
abstract: The phenomenon that caloric restriction increases life span in a variety of species from yeast to mice has been the focus of much interest. Recent observations suggest that a protein important for heterochromatin formation, Sir2, is central for caloric restriction-induced longevity in lower organisms. Interestingly, Sir2 is also capable of repairing DNA double-strand breaks by nonhomologous end joining which may be important, along with proteins that repair breaks by recombinational repair, for minimizing the age-related deleterious effects of DNA damage induced by oxygen by-products of metabolism. I propose that competition between these two distinct functions could influence longevity and the onset of senescence. In addition, sequence and functional similarities between Sir2 and other chromatin metabolism proteins present the possibility that genetic components for longevity and senescence are conserved from yeast to mammals.
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, The University of Texas, Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA. hastye@uthscsa.edu
authors.forename: P
authors.initials: P
authors.lastname: Hasty
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D002149:Energy Intake; D004734:Energy Metabolism; D005090:Exodeoxyribonucleases; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D000072200:Ku Autoantigen; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008322:Mammals; D009687:Nuclear Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053484:RecQ Helicases; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014898:Werner Syndrome / Q000235:genetics; D000071657:Werner Syndrome Helicase; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D015534:Trans-Activators; C081647:high affinity DNA-binding factor, S cerevisiae; D005090:Exodeoxyribonucleases; C087778:SIR2 protein, S cerevisiae; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen