Curcumin is an early-acting stage-specific inducer of extended functional longevity in Drosophila

Larval feeding with curcumin induces an extended health span with significantly increased median and maximum longevities in the adult fly. This phenotype is diet insensitive and shows no additive effect on longevity when combined with an adult dietary restriction (DR) diet, suggesting that curcumin and DR operate via the same or overlapping pathways for this trait. This treatment significantly slows the aging rate so that it is comparable with that of genetically selected long lived animals. The larval treatment also enhances the adult animal's geotactic activity in an additive manner with DR, suggesting that curcumin and DR may use different pathways for different traits. Feeding the drug to adults during only the health span also results in a significantly extended health span with increased median and maximum life span. This extended longevity phenotype is induced only during these stage-specific periods. Feeding adults with the drug over their whole life results in a weakly negative effect on median longevity with no increase in maximum life span. There are no negative effects on reproduction, although larval curcumin feeding increases development time, and also apparently accelerates the normal late-life neuromuscular degeneration seen in the legs. Gene expression data from curcumin-fed larvae shows that the TOR pathway is inhibited in the larvae and the young to midlife adults, although several other genes involved in longevity extension are also affected. These data support the hypothesis that curcumin acts as if it is a DR mimetic nutraceutical. These data also suggest that the search for DR mimetics may be enhanced by the use of stage-specific screening of candidate molecules.