The life-extending effect of dietary restriction requires Foxo3 in mice

Isao Shimokawa*, Toshimitsu Komatsu, Nobutaka Hayashi, Sang Eun Kim, Takuya Kawata, Seongjoon Park, Hiroko Hayashi, Haruyoshi Yamaza, Takuya Chiba, Ryoichi Mori

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


Forkhead box O (Foxo) transcription factors may be involved in the salutary effect of dietary restriction (DR). This study examined the role of Foxo3 in lifespan extension and cancer suppression in DR mice. Wild-type (WT) and Foxo3-knockout heterozygous (+/–) and homozygous (–/–) mice were subjected to a 30% DR regimen initiated at 12 weeks of age. Control mice were fed ad libitum (AL) throughout the study. In contrast to WT mice, DR did not significantly extend the lifespan of Foxo3+/– or Foxo3–/– mice. However, DR reduced the prevalence of tumors at death in WT, Foxo3+/–, and Foxo3–/– mice. These results indicate the necessity of Foxo3 for lifespan extension but not cancer suppression by DR. The findings in Foxo3+/– mice contrast with those in Foxo1+/– mice reported previously by our laboratory suggest differential regulation of cancer and lifespan by DR via Foxo1 and Foxo3.

Original languageEnglish
Pages (from-to)707-709
Number of pages3
JournalAging cell
Issue number4
Publication statusPublished - 2015 Aug
Externally publishedYes


  • Foxo
  • cancer
  • dietary restriction
  • lifespan
  • longevity
  • mouse

ASJC Scopus subject areas

  • Ageing
  • Cell Biology


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