Knock-down of and additively extends lifespan and healthspan in .

Genetic manipulations can ameliorate the aging process and extend the lifespan of model organisms. The aim of this research was to identify novel genetic interventions that promote both lifespan and healthspan, by combining the effects of multiple longevity-associated gene inactivations in . For this, the individual and combined effects of the mutation and of and knock-downs were studied, both in the wild type and mutant backgrounds. We found that besides increasing the lifespan of wild type animals, the knock-down of (starting at L4) also extends the lifespan and healthspan of long-lived mutants. In the background, and impairment exert opposing effects individually, while the deficient animals show a similar lifespan and healthspan as , suggesting that the and effector outcomes converge downstream of DAF-16. By contrast, knock-down did not extend the lifespan of single or double inactivated animals, and was slightly deleterious to healthspan. In conclusion, we report that impairment of and increases lifespan and healthspan in an additive and synergistic manner, respectively, and that this result is not improved by further knocking-down .