{"doi":"10.1101/2021.06.10.447794","title":"Lysosome Lipid Signaling from the Periphery to Neurons Regulates Longevity","abstract":"Abstract Lysosomes are key cellular organelles that metabolize extra- and intracellular substrates. Alterations in lysosomal metabolism are implicated in aging-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate aging remains unclear. Here, we report a fat-to-neuron lipid signaling pathway induced by lysosomal metabolism and its longevity promoting role in Caenorhabditis elegans . We discovered that lysosomal lipolysis in peripheral fat storage tissue up-regulates the neuropeptide signaling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation requires the secretion from the fat storage tissue of a lipid chaperone protein LBP-3 and polyunsaturated fatty acids (PUFAs). LBP-3 binds to specific PUFAs, and acts through a nuclear hormone receptor NHR-49 and neuropeptide NLP-11 in neurons to extend lifespan. Together, these results reveal lysosomes as a signaling hub to coordinate metabolism and aging, and a lysosomal signaling mechanism that mediates intertissue communication to promote longevity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":229583,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"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":619874,"name":"Jonathon Duffy","orcid":null,"position":1,"is_corresponding":false},{"id":827261,"name":"Andrew Folick","orcid":"0000-0002-2093-034X","position":2,"is_corresponding":false},{"id":827262,"name":"Yi-Tang Lee","orcid":"0000-0002-0413-4706","position":3,"is_corresponding":false},{"id":559751,"name":"Pei-Wen Hu","orcid":null,"position":4,"is_corresponding":false},{"id":827263,"name":"Isaiah A.A. Neve","orcid":"0000-0002-0827-6111","position":5,"is_corresponding":false},{"id":827264,"name":"Feng Jin","orcid":"0000-0002-9099-9318","position":6,"is_corresponding":false},{"id":827265,"name":"Qinghao Zhang","orcid":"0000-0002-5744-9859","position":7,"is_corresponding":false},{"id":438231,"name":"Matthew C. Tillman","orcid":"0000-0001-8516-751X","position":8,"is_corresponding":false},{"id":228326,"name":"Youqiong Ye","orcid":"0000-0001-8332-4710","position":9,"is_corresponding":false},{"id":291973,"name":"William B. Mair","orcid":"0000-0002-0661-1342","position":10,"is_corresponding":false},{"id":245732,"name":"Jin Wang","orcid":"0000-0003-3625-7919","position":11,"is_corresponding":false},{"id":13527,"name":"Leng Han","orcid":"0000-0002-7380-2640","position":12,"is_corresponding":false},{"id":74596,"name":"Eric A. Ortlund","orcid":"0000-0001-8855-3029","position":13,"is_corresponding":false},{"id":245729,"name":"Meng C. Wang","orcid":"0000-0002-5898-6007","position":14,"is_corresponding":false},{"id":827590,"name":"Marzia Savini","orcid":null,"position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:55:01.675482Z","pmid":null,"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":[]}