Overexpression of FOXO1 in skeletal muscle does not alter longevity in mice

Tsuyoshi Chiba, Yasutomi Kamei, Takahiko Shimizu, Takuji Shirasawa, Aki Katsumata, Lisa Shiraishi, Satoshi Sugita, Yoshihiro Ogawa, Shinji Miura, Osamu Ezaki

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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 45α, 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 45α, 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.

Original languageEnglish
Pages (from-to)420-428
Number of pages9
JournalMechanisms of Ageing and Development
Issue number7
Publication statusPublished - Jul 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ageing
  • Developmental Biology


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