Feb, 2009
Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C-elegans
NATURE
- ,
- ,
- ,
- Volume
- 457
- Number
- 7230
- First page
- 726
- Last page
- U6
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1038/nature07583
- Publisher
- NATURE PUBLISHING GROUP
Dietary restriction is the most effective and reproducible intervention to extend lifespan in divergent species(1). In mammals, two regimens of dietary restriction, intermittent fasting ( IF) and chronic caloric restriction, have proven to extend lifespan and reduce the incidence of age- related disorders(2). An important characteristic of IF is that it can increase lifespan even when there is little or no overall decrease in calorie intake(2). The molecular mechanisms underlying IF- induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that the low molecular weight GTPase RHEB- 1 has a dual role in lifespan regulation; RHEB- 1 is required for the IF- induced longevity, whereas inhibition of RHEB- 1 mimics the caloric- restriction effects. RHEB- 1 exerts its effects in part by the insulin/ insulin growth factor ( IGF)- like signalling effector DAF- 16 in IF. Our analyses demonstrate that most fasting- induced upregulated genes require RHEB- 1 function for their induction, and that RHEB- 1 and TOR signalling are required for the fasting- induced downregulation of an insulin- like peptide, INS- 7. These findings identify the essential role of signalling by RHEB- 1 in IF- induced longevity and gene expression changes, and suggest a molecular link between the IF- induced longevity and the insulin/ IGF- like signalling pathway.
- Link information
- ID information
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- DOI : 10.1038/nature07583
- ISSN : 0028-0836
- eISSN : 1476-4687
- Pubmed ID : 19079239
- Web of Science ID : WOS:000263064700042