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- W3085143205 abstract "ABSTRACT Aging and immunity are inextricably linked and many genes that extend lifespan also enhance immunoresistance. However, it remains unclear if longevity-enhancing factors modulate immunity and longevity by distinct or shared mechanisms. Here, we demonstrate that the Caenorhabditis elegans pro-longevity factor, NHR-49, also promotes resistance against Pseudomonas aeruginosa , but modulates immunity and longevity by spatially and mechanistically distinct mechanisms. Fenofibrate, an agonist of NHR-49’s mammalian functional homolog, PPARα, enhanced worm immunoresistance in an NHR-49-dependent manner. NHR-49 expression is increased by germline ablation, an intervention that extends lifespan, but lowered by pathogen exposure. NHR-49 acted in multiple somatic tissues to promote longevity, whereas, it’s pro-immunity function was mediated by neuronal expression. The canonical NHR-49 target genes, acs-2 and fmo-2 , were upregulated by germline loss, but infection triggered fmo-2 downregulation and acs-2 upregulation. Interestingly, neither gene conferred resistance against Gram-negative Pseudomonas , unlike their reported roles in immunity against Gram-positive pathogens. Thus, NHR-49 is differentially regulated by interventions that bring about long-term changes (lifespan extension) vs. short-term stress (pathogen exposure) and in response it orchestrates distinct outputs, including pathogen-specific transcriptional programs. Overall, our study demonstrates the independent control of immunity and longevity by a conserved regulatory protein." @default.
- W3085143205 created "2020-09-21" @default.
- W3085143205 creator A5002614871 @default.
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- W3085143205 creator A5065514587 @default.
- W3085143205 creator A5072580732 @default.
- W3085143205 date "2020-09-11" @default.
- W3085143205 modified "2023-09-26" @default.
- W3085143205 title "NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity" @default.
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- W3085143205 doi "https://doi.org/10.1101/2020.09.11.290452" @default.
- W3085143205 hasPublicationYear "2020" @default.
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