RME-1 is required for lifespan extension and increased resistance to stresses associated with decreased insulin/IGF-1-like signaling in Caenorhabditis elegans

The insulin/insulin-like growth factor (IGF)-1 signaling (IIS) pathway is a conserved life span-modulating genetic pathway. Many genes involved in lifespan extension associated with decreased signaling of the IIS pathway have been identified. In the present study, we found a novel gene required for the effect of the IIS pathway on the stress response and aging in C. elegans. Receptor mediated endocytosis (RME)-1 is expressed ubiquitously and known to be involved in cellular endocytic transport. Knockdown of rme-1abolished the lifespan-extending effect caused by decreased IIS. In addition, resistance to oxidative stress, heat shock and ultraviolet irradiation were significantly decreased when the expression of RME-1 was blocked. The delayed age-related decline in motility observed in age-1 mutants with defects in the IIS pathway was also modulated by RME-1. The expression of sod-3, which is positively correlated with the remaining lifespan of an individual, was decreased by rme-1 knockdown. Our study demonstrates that RME-1 is required for the anti-aging effect associated with decreased IIS. We suggest that endocytic transport could be one underlying mechanisms for longevity via the IIS pathway.