Calorie restriction in humans inhibits the PI 3 K / AKT pathway and induces a younger transcription profile
Year: 2013
Type: article
Abstract: 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.
Source: Aging Cell
DOI: 10.1111/acel.12088
Institutions: National Institutes of Health, National Institute on Aging, Washington University in St. Louis, Broad Institute, Howard Hughes Medical Institute, Harvard University, Whitehead Institute for Biomedical Research, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, University of Bologna, University of Salerno, CEINGE Biotecnologie Avanzate Franco Salvatore (Italy)
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: bronze
Funders: Howard Hughes Medical Institute, Longer Life Foundation, Charles A. King Trust, Alvin J. Siteman Cancer Center, Georgia Clinical and Translational Science Alliance, Bakewell Foundation, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1114310655, G299873027, G4467312596, Washington University Institute of Clinical and Translational Sciences, The in vivo regulation of glucose homeostasis and lifespan by mTORC2, Washington University Institute of Clinical and Translational Sciences (UL1), G8242737674, G8343896170, G9000271159, G9000319192, Washington University Nutrition Obesity Research Center, Cancer Center Support Grant, GENERAL CLINICAL RESEARCH CENTER
OpenAlex ID: W2125881727