{"doi":"10.1093/gerona/glae050","title":"Cacao Procyanidins-Induced Lifespan Extension in <i>Caenorhabditis elegans</i> in a Nervous System and CaMKII-Dependent Manner","abstract":"Procyanidins are gaining attention due to their potential health benefits. We found that cacao liquor procyanidin (CLPr) from Theobroma cacao seeds increased the lifespan of Caenorhabditis elegans, a representative model organism for aging studies. The genetic dependence of the lifespan-extending effect of CLPr was consistent with that of blueberry procyanidin, which is dependent on unc-43, osr-1, sek-1, and mev-1, but not on daf-16, sir-2.1, or skn-1. The lifespan-extending effect of CLPr was inhibited by neuron-specific RNA interference (RNAi) targeting unc-43 and pmk-1, and in worms with loss-of-function mutations in the odr-3, odr-1, or tax-4 genes, which are essential in sensory neurons, including AWC neurons. It was also inhibited in worms in which AWC neurons or AIB interneurons had been eliminated, and in worms with loss-of-function mutations in eat-4 or glr-1, which are responsible for glutamatergic synaptic transmission. These results suggest that the lifespan-extending effect of CLPr is dependent on the nervous system. In addition, it also requires unc-43 and pmk-1 expression in nonneuronal cells, as demonstrated by the experiments with RNAi in wild-type worms, the neuronal cells of which are not affected by systemic RNAi. The osr-1 gene is expressed in hypodermal and intestinal cells and regulates the response to osmotic stress along with unc-43/calcium/calmodulin-dependent protein kinase II and the p38 mitogen-activated protein kinase pathway. Consistent with this, CLPr improved osmotic stress tolerance in an unc-43- and pmk-1-dependent manner, and it was also dependent on AWC neurons. The lifespan-extending and osmotic-tolerance-improving activities were attributed to procyanidins with a tetrameric or higher-order oligomeric structure.","journal":"The Journals of Gerontology Series A","year":2024,"id":494437,"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":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1341214,"name":"Yuki Morinaga","orcid":null,"position":1,"is_corresponding":false},{"id":1341215,"name":"Sarina Kobayashi","orcid":null,"position":2,"is_corresponding":false},{"id":1341216,"name":"Aika Matsubara","orcid":null,"position":3,"is_corresponding":false},{"id":1341217,"name":"Kaito Sadanaga","orcid":null,"position":4,"is_corresponding":false},{"id":1341218,"name":"Shuhei Tohtani","orcid":null,"position":5,"is_corresponding":false},{"id":1341219,"name":"Hideaki Saeki","orcid":null,"position":6,"is_corresponding":false},{"id":1341220,"name":"Hiroto Horiuchi","orcid":null,"position":7,"is_corresponding":false},{"id":1341221,"name":"Yuta Fujikawa","orcid":null,"position":8,"is_corresponding":false},{"id":1341002,"name":"Koichiro Sumi","orcid":"0000-0003-4191-1110","position":9,"is_corresponding":false},{"id":1341222,"name":"Midori Natsume","orcid":null,"position":10,"is_corresponding":false},{"id":1341003,"name":"Hideshi Inoue","orcid":"0000-0001-9806-9660","position":11,"is_corresponding":false},{"id":1341213,"name":"Keiya Ohmine","orcid":null,"position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T02:09:11.736910Z","pmid":"38366688","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":[]}