Sirtuins in aging and disease

Cold Spring Harb Symp Quant Biol. 2007;72:483-8. doi: 10.1101/sqb.2007.72.024.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology
  • Caloric Restriction
  • Disease / etiology
  • Humans
  • Mice
  • Mitochondria / metabolism
  • Models, Biological
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology
  • Sirtuin 1
  • Sirtuins / genetics
  • Sirtuins / physiology*

Substances

  • Reactive Oxygen Species
  • SIRT1 protein, human
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Sirtuins