{"doi":"10.1155/2020/4939310","title":"Insulin-Like Growth Factor I Prevents Cellular Aging via Activation of Mitophagy","abstract":"Mitochondrial dysfunction is a hallmark of cellular aging. Mitophagy is a critical mitochondrial quality control mechanism that removes dysfunctional mitochondria and contributes to cell survival. Insulin-like growth factor 1 (IGF-1) promotes survival of smooth muscle cells (SMCs), but its potential effect on cellular aging is unknown yet. We found that IGF-1 decreased cell senescence, prevented DNA telomere shortening, increased mitochondrial membrane potential, activated cytochrome C oxidase, and reduced mitochondrial DNA damage in long-term cultured (aged) aortic SMC, suggesting an antiaging effect. IGF-1 increased mitophagy in aged cells, and this was associated with decreased expression of cyclin-dependent kinase inhibitors p16 and p21 and elevated levels of Nrf2 and Sirt3, regulators of mitophagy and mitochondrial biogenesis. SiRNA-induced inhibition of either Nrf2 or Sirt3 blocked IGF-1-induced upregulation of mitophagy, suggesting that the Nrf2/Sirt3 pathway was required for IGF-1's effect on mitophagy. PINK1 is a master regulator of mitophagy. PINK1 silencing suppressed mitophagy and inhibited IGF-1-induced antiaging effects in aged SMC, consistent with an essential role of mitophagy in IGF-1's effect on cellular aging. Thus, IGF-1 inhibited cellular aging via Nrf2/Sirt3-dependent activation of mitophagy. Our data suggest that activation of IGF-1 signaling is a novel potential strategy to activate mitophagy and slow cellular aging.","journal":"Journal of Aging Research","year":2020,"id":100875,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":494400,"name":"Zhaohui Li","orcid":"0000-0002-4132-658X","position":1,"is_corresponding":false},{"id":275594,"name":"Yusuke Higashi","orcid":"0000-0003-1956-0182","position":2,"is_corresponding":false},{"id":109523,"name":"Patrice Delafontaine","orcid":"0000-0003-3744-3617","position":3,"is_corresponding":false},{"id":275593,"name":"Sergiy Sukhanov","orcid":"0000-0002-9223-4263","position":4,"is_corresponding":false},{"id":495019,"name":"Xuwei Hou","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T22:39:01.863288Z","pmid":"32802505","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":[]}