Figure 3. UNC-62 knockdown extends lifespan in intestinal and hypodermal tissues.

(A) Tissue-specific RNAi is achieved in worms by starting with a strain deficient for the RNAi pathway due to the rde-1(ne219) mutation. A transgene expressing rde-1 under a tissue-specific promoter (examples shown use elt-2 to drive intestine-specific expression, or hlh-1 to drive muscle-specific expression) rescues the RNAi pathway only in the desired tissue. (B) unc-62 RNAi extends lifespan by ∼30% (p<10⁻⁵) in wild-type worms. (C–D) A ∼30% extension is observed when unc-62 is knocked down in (C) a strain expressing rde-1 from the elt-2 intestinal promoter (strain OLB11) or (D) the lin-26 hypodermal promoter (strain NR222). (E–G) In contrast, unc-62 knockdown in (E) neurons and vulval precursor cells (a short unc-62 promoter in an rde-1(ne219);rrf-3(pk1426) background; strain NK742), (F) muscle (hlh-1 promoter; strain NR350), or (G) uterine cells (fos-1A promoter in an rde-1(ne219);rrf-3(pk1426) background; strain NK640) did not significantly extend lifespan (p>0.01). The rrf-3(pk1426) mutation provides increased RNAi sensitivity in neuronal cells. Except for uterine-specific RNAi, lifespans were performed two or more times (Table S2). Lifespan data shown is aggregated from multiple simultaneous experiments.