Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile

Evi M. Mercken, Seth D. Crosby, Dudley W. Lamming, Lellean Jebailey, Susan Krzysik-Walker, Dennis T. Villareal, Miriam Capri, Claudio Franceschi, Yongqing Zhang, Kevin Becker, David M. Sabatini, Rafael de Cabo, Luigi Fontana

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)645-651
Number of pages7
JournalAging Cell
Volume12
Issue number4
DOIs
Publication statusPublished - Aug 2013

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Caloric Restriction
Phosphatidylinositol 3-Kinases
Skeletal Muscle
Insulin
Insulin-Like Growth Factor I
Organelle Biogenesis
Down-Regulation
Inflammation
Health

Keywords

  • Caloric restriction
  • Human
  • Insulin/IGF-1 signaling
  • Skeletal muscle

ASJC Scopus subject areas

  • Cell Biology
  • Ageing

Cite this

Mercken, E. M., Crosby, S. D., Lamming, D. W., Jebailey, L., Krzysik-Walker, S., Villareal, D. T., ... Fontana, L. (2013). Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell, 12(4), 645-651. https://doi.org/10.1111/acel.12088

Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. / Mercken, Evi M.; Crosby, Seth D.; Lamming, Dudley W.; Jebailey, Lellean; Krzysik-Walker, Susan; Villareal, Dennis T.; Capri, Miriam; Franceschi, Claudio; Zhang, Yongqing; Becker, Kevin; Sabatini, David M.; de Cabo, Rafael; Fontana, Luigi.

In: Aging Cell, Vol. 12, No. 4, 08.2013, p. 645-651.

Research output: Contribution to journalArticle

Mercken, EM, Crosby, SD, Lamming, DW, Jebailey, L, Krzysik-Walker, S, Villareal, DT, Capri, M, Franceschi, C, Zhang, Y, Becker, K, Sabatini, DM, de Cabo, R & Fontana, L 2013, 'Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile', Aging Cell, vol. 12, no. 4, pp. 645-651. https://doi.org/10.1111/acel.12088
Mercken EM, Crosby SD, Lamming DW, Jebailey L, Krzysik-Walker S, Villareal DT et al. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell. 2013 Aug;12(4):645-651. https://doi.org/10.1111/acel.12088
Mercken, Evi M. ; Crosby, Seth D. ; Lamming, Dudley W. ; Jebailey, Lellean ; Krzysik-Walker, Susan ; Villareal, Dennis T. ; Capri, Miriam ; Franceschi, Claudio ; Zhang, Yongqing ; Becker, Kevin ; Sabatini, David M. ; de Cabo, Rafael ; Fontana, Luigi. / Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. In: Aging Cell. 2013 ; Vol. 12, No. 4. pp. 645-651.
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