期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 68, 期 2, 页码 108-116出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/gls127
关键词
Rapamycin; Dietary restriction; mTOR; Autophagy; Gene expression
资金
- San Antonio Nathan Shock Aging Center [1P30-AG-13319]
- National Institutes of Health (NIH) [AG036613]
- NIH [AG021890]
- Ellison Medical Foundation
Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin.
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