期刊
NATURE
卷 444, 期 7117, 页码 337-342出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature05354
关键词
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资金
- NIA NIH HHS [R01 AG019719, R37 AG028730, R01 AG019972, R01 AG028730, P01 AG027916] Funding Source: Medline
- NIGMS NIH HHS [R01 GM068072] Funding Source: Medline
Resveratrol ( 3,5,4'- trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle- aged mice on a high- calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin- like growth factor- 1 ( IGF- I) levels, increased AMP- activated protein kinase ( AMPK) and peroxisome proliferator- activated receptor-gamma coactivator 1 alpha ( PGC- 1 alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high- calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity- related disorders and diseases of ageing.
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