{"doi":"10.1111/acel.70058","title":"The Proprotein Convertase <scp>BLI</scp> ‐4 Is Required for Axenic Dietary Restriction Mediated Longevity in <scp> <i>Caenorhabditis elegans</i> </scp>","abstract":"Dietary restriction (DR) is a well-established method for extending lifespan across various species, including C. elegans. Among the different DR regimens, axenic dietary restriction (ADR), in which worms are grown in a nutrient-rich sterile liquid medium, yields the most powerful lifespan extension. However, the molecular mechanisms underlying this longevity phenotype remain largely unexplored. Through a pilot screen of candidate genes, we identified the proprotein convertase BLI-4 as a crucial factor in neurons for modulating lifespan under ADR conditions. BLI-4's role appears to be specific to ADR, as it does not significantly impact longevity under other DR regimens. We further explored the involvement of different bli-4 isoforms and found that isoforms b, f, i and j redundantly contribute to the ADR-mediated lifespan extension, while the bli-4d isoform is mainly involved in development. Proteomics analysis revealed that the loss of BLI-4 function under ADR conditions specifically downregulates GOLG-2, involved in Golgi complex organization. This gene also partially mediates the longevity effects of BLI-4 under ADR conditions. Our findings highlight the importance of neuronal BLI-4 and its downstream targets in regulating lifespan extension induced by ADR in C. elegans.","journal":"Aging Cell","year":2025,"id":550436,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":726638,"name":"Lieselot Vandemeulebroucke","orcid":null,"position":1,"is_corresponding":false},{"id":972869,"name":"Huaihan Cai","orcid":"0000-0002-2580-5767","position":2,"is_corresponding":false},{"id":725999,"name":"Bart P. Braeckman","orcid":"0000-0002-0085-8264","position":3,"is_corresponding":false},{"id":972870,"name":"Ping Wu","orcid":"0000-0002-1136-4892","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:16.596730Z","pmid":"40200707","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":[]}