The MAPK cascades play an important role in many biological processes. However, it is not completely clear whether the MAPK cascades are involved in regulation of the lifespan. To address this, we examined the effect of RNAi inactivation of the genes comprising C. elegans MAPK cascades on lifespan. In the C. elegans genome, there are 36 genes that encode components of the MAPK cascades, including 12 genes of the MAPKKK family, 10 genes of the MAPKK family, and 14 genes of the MAPK family. RNAi inactivation of 6 of these 36 genes caused lifespan extension. The 6 genes include
mlk-1/MLK1,Y105C5A.24/TAK1,
mek-1/MKK7, VZC374L.1/MKK4,
lit-1/NLK and C49C3.10/JNK1. On the other hand, RNAi inactivation of 3 genes (
lin-45/RAF1,
mek-2/MEK2 and
mpk-1/ERK2) caused lifespan shortening. The 3 genes are known to comprise the ERK MAPK cascade in C. elegans. Our results show that the regulation of lifespan by the ERK MAPK cascade is dependent on
daf-16. Taken together, these results demonstrate that several of the MAPK cascades are involved in the regulation of lifespan in C. elegans.