Calorie restriction, SIRT1 and metabolism: understanding longevity

Nat Rev Mol Cell Biol. 2005 Apr;6(4):298-305. doi: 10.1038/nrm1616.


Calorie restriction (CR) is the only experimental manipulation that is known to extend the lifespan of a number of organisms including yeast, worms, flies, rodents and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer and cardiovascular disorders) in mammals. The mechanisms through which this occurs have been unclear. CR induces metabolic changes, improves insulin sensitivity and alters neuroendocrine function in animals. In this review, we summarize recent findings that are beginning to clarify the mechanisms by which CR results in longevity and robust health, which might open new avenues of therapy for diseases of ageing.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Caloric Restriction*
  • Dietary Fats / metabolism
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Insulin / metabolism
  • Longevity / physiology*
  • Mitochondria / metabolism
  • Neurons / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism*


  • Dietary Fats
  • Insulin
  • Sirtuins
  • Histone Deacetylases