Program of the 2004 East Coast Worm Meeting - Caenorhabditis ...

19. Life span regulation by JNK MAP kinase in C. elegans: a novel input into daf-16
Seung Wook Oh, Nenad Svrzikapa, Heidi A. Tissenbaum
Program in Molecular Medicine, University of Massachusetts Medical School, Aaron Lazare
Research Building, 364 Plantation Street, Worcester, MA 01605
The insulin-like signaling plays a pivotal role in life span regulation in many diverse organisms.
In C. elegans, mutations attenuating daf-2, an ortholog of the mammalian insulin and insulin-like
growth factor-1 (IGF-1) receptor, or age-1, the PI 3-kinase catalytic subunit (p110), extend life
span and confer stress resistance. These phenotypes require the FOXO transcription factor
ortholog, DAF-16, which is down regulated by this pathway. Here we show the C. elegans JNK
MAP kinase as a novel input into daf-16 for life span regulation. Overexpression of jnk-1 extends
life span by up to 45%, which requires two upstream kinases, jkk-1 and mek-1. Genetic analysis
indicates that life span extension by jnk-1 overexpression is suppressed by daf-16 RNAi and
synergizes with a mutation in daf-2. In addition, overexpression of jnk-1 promotes resistance to
oxidative and heat stress. Taken together, these findings define a new role for the JNK MAP
kinase signaling pathway in life span regulation and identify a new pathway that targets daf-16.