Sirtuins in aging and disease.
Sirtuin genes function as anti-aging genes in yeast, Caenorhabditis elegans, and Drosophila. The NAD requirement for sirtuin function indicates a link between aging and metabolism, and a boost in sirtuin activity may in part explain how calorie restriction extends life span. In mammals, one of the substrates of the SIR2 ortholog, SIRT1, is a regulator of mitochondrial biogenesis, PGC-1alpha. Indeed, the putative SIRT1 activator resveratrol has been shown to stimulate mitochondrial biogenesis and deliver health benefits in treated mice. I explore here how mitochondrial biogenesis may have beneficial effects on aging and, perhaps, diseases of aging. In particular, I speculate that SIRT1-mediated mitochondrial biogenesis may reduce the production of reactive oxygen species, a possible cause of aging, and offer two possible mechanisms for this effect. An understanding of how calorie restriction works may lead to novel drugs to combat diseases of aging.
Guarente
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Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D031204:Caloric Restriction; D004194:Disease / Q000209:etiology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000502:physiology*
D017382:Reactive Oxygen Species; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins