{"doi":"10.1111/acel.13413","title":"Cell nonautonomous roles of NHR‐49 in promoting longevity and innate immunity","abstract":"Aging and immunity are inextricably linked and many genes that extend life span also enhance immunoresistance. However, it remains unclear whether longevity-enhancing factors modulate immunity and longevity by discrete 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 distinctly. NHR-49 expression increases upon germline ablation, an intervention that extends life span, but was lowered by Pseudomonas infection. The immunosusceptibility induced by nhr-49 loss of function was rescued by neuronal NHR-49 alone, whereas the longevity diminution was rescued by expression in multiple somatic tissues. The well-established NHR-49 target genes, acs-2 and fmo-2, were also differentially regulated following germline elimination or Pseudomonas exposure. Interestingly, neither gene conferred immunity toward Gram-negative Pseudomonas, unlike their known functions against gram-positive pathogens. Instead, genes encoding antimicrobial factors and xenobiotic-response proteins upregulated by NHR-49 contributed to resistance against Pseudomonas. Thus, NHR-49 is differentially regulated by interventions that bring about long-term changes (life span extension) versus short-term stress (pathogen exposure) and in response it orchestrates discrete outputs, including pathogen-specific transcriptional programs.","journal":"Aging Cell","year":2021,"id":162913,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":392135,"name":"Francis R. G. Amrit","orcid":"0000-0003-1928-3234","position":1,"is_corresponding":false},{"id":380505,"name":"Ramesh Ratnappan","orcid":"0000-0001-7055-9043","position":2,"is_corresponding":false},{"id":682511,"name":"Nicholas DelBuono","orcid":null,"position":3,"is_corresponding":false},{"id":681408,"name":"Julia A. Loose","orcid":"0000-0001-6226-9177","position":4,"is_corresponding":false},{"id":392144,"name":"Arjumand Ghazi","orcid":"0000-0002-5859-4206","position":5,"is_corresponding":false},{"id":681407,"name":"Nikki Naim","orcid":"0000-0002-2005-7202","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T23:45:17.971865Z","pmid":"34156142","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}