PMID- 23601134
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20211021
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 12
IP  - 4
DP  - 2013 Aug
TI  - Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger 
      transcription profile.
PG  - 645-51
LID - 10.1111/acel.12088 [doi]
AB  - 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.
CI  - (c) 2013 John Wiley & Sons Ltd and the Anatomical Society.
FAU - Mercken, Evi M
AU  - Mercken EM
AD  - Laboratory of Experimental Gerontology, National Institute on Aging, National 
      Institutes of Health, Baltimore, MD 21224, USA.
FAU - Crosby, Seth D
AU  - Crosby SD
FAU - Lamming, Dudley W
AU  - Lamming DW
FAU - JeBailey, Lellean
AU  - JeBailey L
FAU - Krzysik-Walker, Susan
AU  - Krzysik-Walker S
FAU - Villareal, Dennis T
AU  - Villareal DT
FAU - Capri, Miriam
AU  - Capri M
FAU - Franceschi, Claudio
AU  - Franceschi C
FAU - Zhang, Yongqing
AU  - Zhang Y
FAU - Becker, Kevin
AU  - Becker K
FAU - Sabatini, David M
AU  - Sabatini DM
FAU - de Cabo, Rafael
AU  - de Cabo R
FAU - Fontana, Luigi
AU  - Fontana L
LA  - eng
SI  - GEO/GSE38063
GR  - M01 RR000036/RR/NCRR NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - UL1 TR000448/TR/NCATS NIH HHS/United States
GR  - K99 AG041765/AG/NIA NIH HHS/United States
GR  - P30 DK056341/DK/NIDDK NIH HHS/United States
GR  - P30DK056341/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024992/RR/NCRR NIH HHS/United States
GR  - P30 CA91842/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130605
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (FOXO3 protein, human)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Adipose Tissue/cytology/metabolism
MH  - Adult
MH  - Aging
MH  - Animals
MH  - *Caloric Restriction
MH  - Female
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/genetics/metabolism
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Mitochondrial Turnover
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Principal Component Analysis
MH  - Quadriceps Muscle/cytology/metabolism
MH  - Rats
MH  - *Signal Transduction
MH  - *Transcription, Genetic
MH  - *Transcriptome
PMC - PMC3714316
MID - NIHMS471911
OTO - NOTNLM
OT  - caloric restriction
OT  - human
OT  - insulin/IGF-1 signaling
OT  - skeletal muscle
COIS- Conflict of interest The authors declare no conflicts of interest.
EDAT- 2013/04/23 06:00
MHDA- 2013/12/18 06:00
PMCR- 2014/08/01
CRDT- 2013/04/23 06:00
PHST- 2013/04/12 00:00 [accepted]
PHST- 2013/04/23 06:00 [entrez]
PHST- 2013/04/23 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - 10.1111/acel.12088 [doi]
PST - ppublish
SO  - Aging Cell. 2013 Aug;12(4):645-51. doi: 10.1111/acel.12088. Epub 2013 Jun 5.