A Nuclear Hormone Receptor nhr-76 Induces Age-Dependent Chemotaxis Decline in C. elegans

A decline in food-searching behavior of post-reproductive animals can benefit the population and possibly be programmed by the genome despite its detrimental effect on an individual. We investigated the genetic program of age-dependent decline in chemotaxis behavior toward an odorant secreted from bacterial food in C. elegans. Through a novel forward genetic screen, we identified the gene encoding a nuclear hormone receptor, nhr-76, whose mutants ameliorate the age-dependent chemotaxis decline. We found that NHR-76 downregulates odorant receptor expression during aging in a ligand-binding-domain-dependent manner. Since NHR-76 expression and localization remain unchanged with age, its activity may be modulated through the ligand-binding domain, leading to age-dependent chemotaxis decline. Our findings imply that post-reproductive behavioral decline can be genetically programmed.