PMID- 19426753
OWN - NLM
STAT- MEDLINE
DCOM- 20090818
LR  - 20201209
IS  - 1872-6216 (Electronic)
IS  - 0047-6374 (Linking)
VI  - 130
IP  - 7
DP  - 2009 Jul
TI  - Overexpression of FOXO1 in skeletal muscle does not alter longevity in mice.
PG  - 420-8
LID - 10.1016/j.mad.2009.04.004 [doi]
AB  - Caloric restriction (CR) is the most robust and reproducible intervention that 
      can extend lifespan in rodents. Studies in invertebrates have led to the 
      identification of genes that regulate lifespan, some of which encode components 
      of the insulin or insulin-like signaling pathway, including DAF-16 (C. elegans) 
      and dFOXO (Drosophila). Mice subjected to CR for 8 weeks showed an increase in 
      FOXO1 mRNA and other longevity-related genes: Gadd 45alpha, glutamine synthase, 
      and catalase in skeletal muscle. To investigate whether FOXO1 expression affects 
      longevity in mammals, transgenic mice were studied that over-express FOXO1 in 
      their skeletal muscle (FOXO1 mice), and in which muscle atrophy occurs. FOXO1 
      mice showed increases in Gadd 45alpha, and glutamine synthase proteins in 
      skeletal muscle. In FOXO1 mice, the phosphorylation/dephosphorylation state of 
      the p70 S6K and 4E-BP1 proteins were not altered, suggesting that translation 
      initiation of protein synthesis might not be suppressed. The lifespan of FOXO1 
      mice was similar to their wild-type littermates. FOXO1 overexpression could not 
      prevent aging-induced reduction in catalase, CuZu-SOD, and Mn-SOD mRNA in 
      skeletal muscle. These data suggest that an increase in FOXO1 protein and its 
      activation in skeletal muscle does not extend lifespan in mice.
FAU - Chiba, Tsuyoshi
AU  - Chiba T
AD  - Nutritional Science Program, National Institute of Health and Nutrition, 
      Shinjuku-ku, Tokyo, Japan.
FAU - Kamei, Yasutomi
AU  - Kamei Y
FAU - Shimizu, Takahiko
AU  - Shimizu T
FAU - Shirasawa, Takuji
AU  - Shirasawa T
FAU - Katsumata, Aki
AU  - Katsumata A
FAU - Shiraishi, Lisa
AU  - Shiraishi L
FAU - Sugita, Satoshi
AU  - Sugita S
FAU - Ogawa, Yoshihiro
AU  - Ogawa Y
FAU - Miura, Shinji
AU  - Miura S
FAU - Ezaki, Osamu
AU  - Ezaki O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090506
PL  - Ireland
TA  - Mech Ageing Dev
JT  - Mechanisms of ageing and development
JID - 0347227
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxo1 protein, mouse)
RN  - 0 (Gadd45a protein, mouse)
RN  - 0 (Muscle Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.4.1.13 (Glutamate Synthase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Caloric Restriction
MH  - Carrier Proteins/genetics/metabolism
MH  - Catalase/genetics/metabolism
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - Eukaryotic Initiation Factors
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/*biosynthesis/genetics
MH  - *Gene Expression Regulation
MH  - Glutamate Synthase/genetics/metabolism
MH  - Longevity/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle Proteins/*biosynthesis/genetics
MH  - Muscle, Skeletal/*metabolism
MH  - Nuclear Proteins/genetics/metabolism
MH  - Peptide Chain Initiation, Translational/physiology
MH  - Phosphoproteins/genetics/metabolism
MH  - Phosphorylation/physiology
MH  - RNA, Messenger/biosynthesis
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - Superoxide Dismutase/genetics/metabolism
EDAT- 2009/05/12 09:00
MHDA- 2009/08/19 09:00
CRDT- 2009/05/12 09:00
PHST- 2008/08/20 00:00 [received]
PHST- 2009/04/15 00:00 [revised]
PHST- 2009/04/17 00:00 [accepted]
PHST- 2009/05/12 09:00 [entrez]
PHST- 2009/05/12 09:00 [pubmed]
PHST- 2009/08/19 09:00 [medline]
AID - S0047-6374(09)00054-2 [pii]
AID - 10.1016/j.mad.2009.04.004 [doi]
PST - ppublish
SO  - Mech Ageing Dev. 2009 Jul;130(7):420-8. doi: 10.1016/j.mad.2009.04.004. Epub 2009 
      May 6.