期刊
PLOS ONE
卷 5, 期 3, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0009468
关键词
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资金
- Associazione Italiana per la Ricerca sul Cancro [4874]
- European Community
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR)
- Cariplo Foundation
- Ferrari Foundation
- Monzino Foundation
- Bundesministerium fuer Bildung und Forschung [01GS0869, 01GS0851, 01GS0850]
- [LSHG-2006-037188]
Background: In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Methodology/Principal Findings: Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age-or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length. Conclusions/Significance: Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice.
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