biostudies-literatureYokosawa RJST SPRINGDaiko FoundationJSTJapan Science and Technology AgencyJSPSJapan Society for the Promotion of Sciencee70277https://www.ebi.ac.uk/biostudies/studies/S-EPMC12686552biostudies-literatureUnknown24(12)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.Aging cellA Nuclear Hormone Receptor nhr-76 Induces Age-Dependent Chemotaxis Decline in C. elegans.PMC12686552JPMJSP2125JPMJFR 214VNo.9286JP 21K06014Yokosawa RNoma KfalseA 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.2025-01-01T00:00:00Z2025 Dec2026-05-23T03:25:51.841Z2026-05-23T03:13:50.896ZS-EPMC126865524112844110.1111/acel.70277