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

doi:10.1111/acel.12340

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

Research output: Contribution to journal › Article › peer-review

47 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	707-709
Number of pages	3
Journal	Aging cell
Volume	14
Issue number	4
DOIs	https://doi.org/10.1111/acel.12340
Publication status	Published - 2015 Aug 1
Externally published	Yes

Keywords

Foxo
cancer
dietary restriction
lifespan
longevity
mouse

ASJC Scopus subject areas

Ageing
Cell Biology

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10.1111/acel.12340

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title = "The life-extending effect of dietary restriction requires Foxo3 in mice",

abstract = "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.",

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author = "Isao Shimokawa and Toshimitsu Komatsu and Nobutaka Hayashi and Kim, {Sang Eun} and Takuya Kawata and Seongjoon Park and Hiroko Hayashi and Haruyoshi Yamaza and Takuya Chiba and Ryoichi Mori",

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AU - Shimokawa, Isao

AU - Komatsu, Toshimitsu

AU - Hayashi, Nobutaka

AU - Kim, Sang Eun

AU - Kawata, Takuya

AU - Park, Seongjoon

AU - Hayashi, Hiroko

AU - Yamaza, Haruyoshi

AU - Chiba, Takuya

AU - Mori, Ryoichi

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

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