Feeding rapamycin extended fly lifespan through autophagy and reduced translation, and worked even in flies already on a lifespan-maximizing diet.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Drosophila melanogaster |
| Journal | Cell Metabolism |
| Year | 2010 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cmet.2009.11.010 · PMID 20074526 · Free full text (PMC2824086) |
The target of rapamycin (TOR) pathway is a major nutrient-sensing pathway that, when genetically downregulated, increases life span in evolutionarily diverse organisms including mammals. The central component of this pathway, TOR kinase, is the target of the inhibitory drug rapamycin, a highly specific and well-described drug approved for human use. We show here that feeding rapamycin to adult Drosophila produces the life span extension seen in some TOR mutants. Increase in life span by rapamycin was associated with increased resistance to both starvation and paraquat. Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation. Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms.
| Intervention | Rapamycin (feeding) |
| Target | TOR |
| Model | Drosophila melanogaster |
| Effect | Feeding rapamycin extends fly lifespan via autophagy and reduced translation |