title: Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile.
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.
authors.affiliation: Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Evi M
authors.initials: EM
authors.lastname: Mercken
authors.forename: Seth D
authors.initials: SD
authors.lastname: Crosby
authors.forename: Dudley W
authors.initials: DW
authors.lastname: Lamming
authors.forename: Lellean
authors.initials: L
authors.lastname: JeBailey
authors.forename: Susan
authors.initials: S
authors.lastname: Krzysik-Walker
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Villareal
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kevin
authors.initials: K
authors.lastname: Becker
authors.forename: David M
authors.initials: DM
authors.lastname: Sabatini
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D000375:Aging; D000818:Animals; D031204:Caloric Restriction; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D063269:Mitochondrial Turnover; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D025341:Principal Component Analysis; D052097:Quadriceps Muscle / Q000166:cytology / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases
keywords: caloric restriction; human; insulin/IGF-1 signaling; skeletal muscle