Related Experiment Video
Updated: Apr 15, 2026
Solid Plate-based Dietary Restriction in Caenorhabditis elegans
Published on: May 28, 2011
The life-extending effect of dietary restriction requires Foxo3 in mice
Isao Shimokawa1, Toshimitsu Komatsu1, Nobutaka Hayashi1
1Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
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.
Insights
Dietary restriction (DR) extends lifespan in wild-type mice, but not in Foxo3-knockout mice. DR suppresses tumors in all groups, indicating Foxo3 is essential for DR-mediated lifespan extension, but not cancer suppression.
Area of Science:
- Aging research
- Genetics
- Molecular biology
Background:
- Dietary restriction (DR) is known to extend lifespan and suppress cancer.
- Forkhead box O (Foxo) transcription factors are implicated in the beneficial effects of DR.
- The specific role of Foxo3 in DR-induced longevity and cancer prevention remains unclear.
Purpose of the Study:
- To investigate the role of Foxo3 in lifespan extension and cancer suppression under DR conditions.
- To compare the effects of DR on lifespan and tumor prevalence in wild-type (WT) and Foxo3-knockout mice.
- To elucidate the differential roles of Foxo1 and Foxo3 in DR-mediated health benefits.
Main Methods:
- Wild-type (WT), Foxo3 heterozygous ((+/-)), and homozygous ((-/-)) mice were subjected to 30% DR or ad libitum (AL) feeding.
- Lifespan and tumor prevalence at death were monitored throughout the study.
- Statistical analyses were performed to compare outcomes between genotypes and dietary conditions.
Main Results:
- DR significantly extended lifespan in WT mice but not in Foxo3(+/-) or Foxo3(-/-) mice.
- DR reduced tumor prevalence at death in WT, Foxo3(+/-), and Foxo3(-/-) mice.
- Findings suggest Foxo3 is necessary for DR-induced lifespan extension but not for tumor suppression.
Conclusions:
- Foxo3 is essential for the lifespan-extending effects of dietary restriction.
- Dietary restriction suppresses cancer independently of Foxo3.
- Differential roles of Foxo1 and Foxo3 in mediating the effects of DR on lifespan and cancer warrant further investigation.
