SIR2: a potential target for calorie restriction mimetics

Trends Mol Med. 2007 Feb;13(2):64-71. doi: 10.1016/j.molmed.2006.12.004. Epub 2007 Jan 4.


Calorie restriction (CR) extends lifespan in a wide variety of species and mitigates diseases of aging in mammals. Here, we describe the evidence that the silent information regulator 2 (SIR2) gene, which encodes a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, regulates lifespan and mediates CR in lower species such as Saccharomyces cerevisiae and Caenorhabditis elegans. We discuss the emerging roles of mammalian SIR2 homologs in regulating physiological changes triggered by CR and their potential connections to diseases of aging. We conclude with the recent advances on small molecules that activate the enzymatic activity of SIR2 as potential CR mimetics. The SIR2 family represents an evolutionarily conserved lifespan regulator. Modulating the activity of SIR2 might provide effective CR mimetics to combat diseases of aging.

Publication types

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

MeSH terms

  • Aging / drug effects
  • Aging / physiology
  • Animals
  • Caenorhabditis elegans / physiology
  • Caloric Restriction*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Longevity / drug effects
  • Longevity / physiology
  • Metabolic Syndrome / etiology
  • Models, Biological
  • Nerve Degeneration / etiology
  • Resveratrol
  • Saccharomyces cerevisiae / physiology
  • Sirtuins / drug effects
  • Sirtuins / physiology*
  • Stilbenes / pharmacology


  • Enzyme Inhibitors
  • Stilbenes
  • Sirtuins
  • Resveratrol