A nuclear hormone receptor regulating nutrient sensing acts as a somatic checkpoint governing reproduction and lifespan in Caenorhabditis elegans, according to a peer-reviewed study published in Nature Communications.
The receptor, known as NHR-49, is a homolog of mammalian PPARα and HNF4α that controls transcriptional regulation of fatty acid metabolism. Researchers found that loss of NHR-49 triggers inappropriate oocyte activation and leads worms to lay unfertilized oocytes when sperm is absent. This abnormal activation causes a rapid depletion of yolk and stored fat, substantially shortening the animal's lifespan.
Preventing yolk transfer into the oocytes largely restored fat storage in nhr-49 mutants and partially rescued their lifespan. The experiments showed that NHR-49 functions primarily within somatic cells, rather than inside the germline itself, to control oocyte activation and ovulation.
The study also demonstrated that NHR-49 couples germline proliferation directly to nutritional conditions. Worms require the receptor to halt germline cell division during periods of starvation.
Genomic analyses identified GSA-1, a G protein alpha s subunit (Gαs), as a direct transcriptional target of NHR-49. The research was conducted by co-lead authors Sharada Gopal and Amaresh Chaturbedi alongside senior author Siu Sylvia Lee at Cornell University's Department of Molecular Biology and Genetics, supported by grants from the National Institute on Aging and the National Institutes of Health.
