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

被引：185

作者：

Mercken, Evi M. ^{[1
]}

Crosby, Seth D. ^{[2
]}

Lamming, Dudley W. ^{[3
,4
,5
,6
,7
]}

JeBailey, Lellean ^{[8
]}

Krzysik-Walker, Susan ^{[9
]}

Villareal, Dennis T. ^{[10
]}

Capri, Miriam ^{[11
,12
]}

Franceschi, Claudio ^{[11
,12
]}

Zhang, Yongqing ^{[13
]}

Becker, Kevin ^{[13
]}

Sabatini, David M. ^{[3
,4
,5
,6
,7
]}

de Cabo, Rafael ^{[1
]}

Fontana, Luigi ^{[10
,14
,15
]}

机构：

[1] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA

[2] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA

[3] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[4] MIT, Dept Biol, Cambridge, MA 02139 USA

[5] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[6] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA

[7] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[8] GeneGo Inc, St Joseph, MI 49085 USA

[9] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA

[10] Washington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63108 USA

[11] Univ Bologna ALMA MATER STUDIORUM, CIG, I-40126 Bologna, Italy

[12] Univ Bologna ALMA MATER STUDIORUM, Dept Expt Diagnost & Specialty Med, I-40126 Bologna, Italy

[13] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA

[14] Univ Salerno, Sch Med, Dept Med, I-84081 Salerno, Italy

[15] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy

来源：

AGING CELL | 2013年 / 12卷 / 04期

基金：

美国国家卫生研究院;

关键词：

caloric restriction; human; insulin; IGF-1; signaling; skeletal muscle; GENE SET ENRICHMENT; ENDURANCE EXERCISE; LONG;

D O I：

10.1111/acel.12088

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：645 / 651

页数：7

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