Calorie restriction in humans inhibits the <scp>PI</scp>3<scp>K</scp>/<scp>AKT</scp> pathway and induces a younger transcription profile

Aging Cell - Tập 12 Số 4 - Trang 645-651 - 2013
Evi M. Mercken1, Seth D. Crosby2, Dudley W. Lamming3,4,5,6,7, Lellean JeBailey8, Susan M. Krzysik-Walker9, Dennis T. Villareal10, Miriam Capri11,12, Claudio Franceschi11,12, Yongqing Zhang13, Kevin G. Becker13, David M. Sabatini3,4,5,6,7, Rafael de Cabo1, Luigi Fontana14,15,10
1Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
2Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA
3Broad Institute of Harvard and MIT, Seven Cambridge Center, Cambridge, MA, 02142 USA
4Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
5Howard Hughes Medical Institute, MIT, Cambridge, MA 02139, USA
6The David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA
7Whitehead Institute for Biomedical Research, Cambridge, MA 02142 USA
8GeneGo, Inc., St. Joseph, MI 49085, USA
9Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
10Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, 63108 USA
11Department of Experimental Diagnostic and Specialty Medicine University of Bologna‐ ALMA MATER STUDIORUM Bologna 40126 Italy
12Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna- ALMA MATER STUDIORUM, Bologna, 40126 Italy
13Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA
14CEINGE Biotecnologie Avanzate, Napoli 80145, Italy
15Department of Medicine, Salerno University Medical School, Salerno, 84081, Italy

Tóm tắt

SummaryCaloric 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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