Diabetes Metab J.  2014 Oct;38(5):321-329. 10.4093/dmj.2014.38.5.321.

Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation

  • 1Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China. yuwanghk@hku.hk


Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension.


Biotin; Dietary restriction; NAD; Nicotinamide; Lifespan; Sirtuins

MeSH Terms

Caloric Restriction*
Cardiovascular Diseases
Risk Factors


  • Fig. 1 In response to different dietary intake, a number of nutrient sensing pathways are activated or inactivated to modulate the ageing process. IGF, insulin-like growth factor; SIRT1, Sir2-like protein 1; AMPK, AMP-activated protein kinase; mTOR/S6K, mammalian target of rapamycin/ribosomal protein S6 kinase; ROS, reactive oxygen species; AKT/PKB, AKT/protein kinase B.

  • Fig. 2 A number of molecular links, including nicotinamide adenine dinucleotide (NAD), niacin, biotin, and related metabolites, are important conduits mediating caloric restriction-induced Sir2/Sir2-like protein 1 (SIRT1) activation and lifespan extension. polyADPR, poly ADP-ribose.


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