Sakiko Honjo et al. (2004) East Asia Worm Meeting "The low molecular weight GTPase Rheb regulates both body size and lifespan"

Sakiko Honjo, Eisuke Nishida

[East Asia Worm Meeting, 2004]

Recent studies in Drosophila and mouse have suggested the relationship between the reduced body size and the increased lifespan, but it is unclear whether this relationship is a causal one. To ask whether both the body size and the lifespan are regulated by a common mechanism, we focused on the low molecular weight GTPase Rheb in C. elegans. Rheb is an evolutionarily conserved gene. In mammalian cells, Rheb is shown to be positively regulated by insulin/IGF signaling and to function to activate the TOR/S6 kinase (S6K) pathway, but the function of Rheb in C.elegans has not been examined. We have identified F54C8.5 as C. elegans Rheb (Ce Rheb). We examined expression of Ce Rheb using a Ce Rheb-GFP fusion construct and found that it was expressed in intestine and neurons. Then we performed Ce Rheb RNAi experiments and found that Ce Rheb RNAi caused marked reduction in the body size. This result is consistent with the reduced body size of Rheb heterozygous mutants in Drosophila, suggesting the conserved function of Rheb in regulating the body size. We then performed Ce Rheb RNAi and Ce S6K RNAi from young adult stages. Ce Rheb RNAi decreased lifespan, whereas Ce S6K RNAi did not. We are examining the role of other components of the Rheb/TOR/S6K pathway in body size and lifespan.