{"doi":"10.1016/j.exger.2024.112495","title":"The Citrus flavanone naringenin prolongs the lifespan in C. elegans and slows signs of brain aging in mice","abstract":"Aging is one of the main risk factors for neurodegenerative disorders, which represent a global burden on healthcare systems. Therefore, identifying new strategies to slow the progression of brain aging is a compelling challenge. In this article, we first assessed the potential anti-aging effects of the Citrus flavanone naringenin (NAR), an activator of the enzyme sirtuin-1 (SIRT1), in a 3R-compliant and short-lived aging model ( i.e. , the nematode C. elegans ). Then, we investigated the preventive effects of a 6-month treatment with NAR (100 mg/kg, orally) against brain aging and studied its mechanism of action in middle-aged mice. We demonstrated that NAR (100 μM) extends lifespan and improves healthspan in C. elegans . In the brain of middle-aged mice, NAR promotes the activity of metabolic enzymes (citrate synthase, cytochrome C oxidase) and increases the expression of the SIRT1 enzyme. Consistently, NAR up-regulates the expression of downstream antioxidant ( Foxo3, Nrf2, Ho-1 ), anti-senescence ( p16 ), and anti-inflammatory ( Il-6, Il-18 ) markers. Our findings support NAR supplementation to slow the signs of brain aging. • Aging is a main risk factor for neurodegenerative diseases. • Sirtuin 1 (SIRT1) enzyme and downstream targets are crucial in the aging process. • The Citrus flavonoid naringenin (NAR) is a SIRT1 activator. • NAR extends the lifespan and improves the healthspan in C. elegans . • Chronic supplementation with NAR slows signs of brain aging in mice.","journal":"Experimental Gerontology","year":2024,"id":428204,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"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":1229403,"name":"Martina De Felice","orcid":"0000-0001-7704-8705","position":1,"is_corresponding":false},{"id":1229404,"name":"Lorenzo Germelli","orcid":"0000-0002-7318-7545","position":2,"is_corresponding":false},{"id":371478,"name":"Vanessa Brinkmann","orcid":"0000-0002-2284-3143","position":3,"is_corresponding":false},{"id":932823,"name":"Lorenzo Flori","orcid":"0000-0001-7899-0954","position":4,"is_corresponding":false},{"id":709908,"name":"Claudia Martini","orcid":"0000-0001-9379-3027","position":5,"is_corresponding":false},{"id":933330,"name":"Vincenzo Calderone","orcid":null,"position":6,"is_corresponding":false},{"id":371480,"name":"Natascia Ventura","orcid":"0000-0001-8718-4321","position":7,"is_corresponding":false},{"id":1229405,"name":"Eleonora Da Pozzo","orcid":"0000-0003-4762-8949","position":8,"is_corresponding":false},{"id":932822,"name":"Lara Testai","orcid":"0000-0003-2431-6248","position":9,"is_corresponding":false},{"id":1229402,"name":"Eugenia Piragine","orcid":"0000-0001-6558-3065","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:58:57.592578Z","pmid":"38897393","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":[]}