期刊
AGING CELL
卷 12, 期 4, 页码 645-651出版社
WILEY
DOI: 10.1111/acel.12088
关键词
caloric restriction; human; insulin; IGF-1 signaling; skeletal muscle
资金
- AFAR (American Federation for Aging Research)
- National Center for Research Resources [UL1 RR024992]
- National Institute of Diabetes And Digestive And Kidney Diseases [P30DK056341]
- National Institute on Aging-Intramural Research Program
- Longer Life Foundation (an RGA/Washington University Partnership)
- Bakewell Foundation
- NCI Cancer Center Support Grant [P30 CA91842]
- ICTS/CTSA Grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1RR024992]
- NIH Roadmap for Medical Research
Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age-related diseases and promote health in humans.
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