Are sirtuins viable targets for improving healthspan and lifespan?

被引：342

作者：

Baur, Joseph A. ^{[1
,2
]}

Ungvari, Zoltan ^{[3
]}

Minor, Robin K. ^{[4
]}

Le Couteur, David G. ^{[5
,6
,7
]}

de Cabo, Rafael ^{[4
]}

机构：

[1] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA

[2] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Stanton L Young Biomed Res Ctr 1303, Oklahoma City, OK 74104 USA

[4] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[5] Univ Sydney, CERA, Sydney, NSW 2139, Australia

[6] Univ Sydney, ANZAC Res Inst, Sydney, NSW 2139, Australia

[7] Concord RG Hosp, Sydney, NSW 2139, Australia

来源：

NATURE REVIEWS DRUG DISCOVERY | 2012年 / 11卷 / 06期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

SMALL-MOLECULE ACTIVATORS; FATTY-ACID OXIDATION; SMOOTH-MUSCLE-CELLS; STIMULATED INSULIN-SECRETION; APOLIPOPROTEIN E-DEFICIENT; RED WINE CONSTITUENT; AGGREGATION IN-VIVO; ALL-CAUSE MORTALITY; CALORIE RESTRICTION; SIRT1; ACTIVATION;

D O I：

10.1038/nrd3738

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：443 / 461

页数：19

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