Are sirtuins viable targets for improving healthspan and lifespan?
Although the increased lifespan of our populations illustrates the success of modern medicine, the risk of developing many diseases increases exponentially with old age. Caloric restriction is known to retard ageing and delay functional decline as well as the onset of disease in most organisms. Studies have implicated the sirtuins (SIRT1-SIRT7) as mediators of key effects of caloric restriction during ageing. Two unrelated molecules that have been shown to increase SIRT1 activity in some settings, resveratrol and SRT1720, are excellent protectors against metabolic stress in mammals, making SIRT1 a potentially appealing target for therapeutic interventions. This Review covers the current status and controversies surrounding the potential of sirtuins as novel pharmacological targets, with a focus on SIRT1.
Department of Physiology and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. baur@mail.med.upenn.edu
Joseph A
JA
Baur
Zoltan
Z
Ungvari
Robin K
RK
Minor
David G
DG
Le Couteur
Rafael
R
de Cabo
D000375:Aging / Q000502:physiology; D000818:Animals; D001711:Biotransformation / Q000502:physiology; D031204:Caloric Restriction; D005853:Geriatrics; D006262:Health; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D008017:Life Expectancy; D008322:Mammals; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism / Q000502:physiology; D056566:Sirtuin 3 / Q000502:physiology; D037761:Sirtuins / Q000187:drug effects / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology
D006576:Heterocyclic Compounds, 4 or More Rings; C525422:SRT1720; D013267:Stilbenes; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D037761:Sirtuins; D000077185:Resveratrol