Open AccessCalorie restriction in humans inhibits the PI 3 K / AKT pathway and induces a younger transcription profile
Author(s) -
Mercken Evi M.,
Crosby Seth D.,
Lamming Dudley W.,
JeBailey Lellean,
KrzysikWalker Susan,
Villareal Dennis T.,
Capri Miriam,
Franceschi Claudio,
Zhang Yongqing,
Becker Kevin,
Sabatini David M.,
Cabo Rafael,
Fontana Luigi
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12088
Subject(s) - biology , mitochondrial biogenesis , calorie restriction , skeletal muscle , microbiology and biotechnology , signal transduction , longevity , pi3k/akt/mtor pathway , endocrinology , mitochondrion , genetics
Summary 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.