Genes and pathways that influence longevity in Caenorhabditis elegans

Abstract

The roundworm Caenorhabditis elegans is one of the most popular model organisms for research on aging because of its short lifespan and genetic tractability. Studies using C. elegans have identified many genes and pathways that regulate aging, several of which are conserved in other species, including mammals. In this chapter, we describe longevity-regulatory pathways including insulin/IGF-1 (insulin-like growth factor 1) signaling, TOR (target of rapamycin) signaling, autophagy, mitochondrial respiration, and HIF-1 (hypoxia-inducible factor 1) pathways. We also review the effects of dietary restriction, a key environmental factor that influences aging, on longevity-regulatory genetic factors. In addition, we illustrate the roles of two important C. elegans tissues, those of the sensory neural and reproductive systems, in regulating longevity at the molecular level. For each of the subtopics, we explain how changes in the expression of genes involved in each pathway and system alter longevity.We also speculate on the evolutionary significance of the genes and pathways that affect longevity. Given the conserved nature of longevity regulation, the dissection of the roles of these genetic factors in determining the C. elegans lifespan will provide important clues for understanding the secrets of human aging.