{"doi":"10.1016/j.jcmgh.2023.06.002","title":"Insulin-Like Growth Factor1 Preserves Gastric Pacemaker Cells and Motor Function in Aging via ERK1/2 Activation","abstract":"BACKGROUND & AIMS: Impaired gastric motor function in the elderly causes reduced food intake leading to frailty and sarcopenia. We previously found that aging-related impaired gastric compliance was mainly owing to depletion of interstitial cells of Cajal (ICC), pacemaker cells, and neuromodulator cells. These changes were associated with reduced food intake. Transformation-related protein 53-induced suppression of extracellular signal-regulated protein kinase (ERK)1/2 in ICC stem cell (ICC-SC) cell-cycle arrest is a key process for ICC depletion and gastric dysfunction during aging. Here, we investigated whether insulin-like growth factor 1 (IGF1), which can activate ERK in gastric smooth muscles and invariably is reduced with age, could mitigate ICC-SC/ICC loss and gastric dysfunction in klotho mice, a model of accelerated aging. METHODS: recombinant human (rh) IGF1 (150 μg/kg intraperitoneally twice daily for 3 weeks). Gastric ICC/ICC-SC and signaling pathways were studied by flow cytometry, Western blot, and immunohistochemistry. Gastric compliance was assessed in ex vivo systems. Transformation-related protein 53 was induced with nutlin 3a and ERK1/2 signaling was activated by rhIGF-1 in the ICC-SC line. RESULTS: rhIGF1 was verified by in vivo systems. In ICC-SC cultures, rhIGF1 mitigated nutlin 3a-induced reduced ERK1/2 phosphorylation and cell growth arrest. CONCLUSIONS: IGF1 can mitigate age-related ICC/ICC-SC loss by activating ERK1/2 signaling, leading to improved gastric compliance and increased food intake in klotho mice.","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2023,"id":352670,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":889398,"name":"Negar Taheri","orcid":"0000-0001-9802-0971","position":1,"is_corresponding":false},{"id":1060638,"name":"Egan L. Choi","orcid":"0000-0002-1258-0896","position":2,"is_corresponding":false},{"id":256714,"name":"Todd A. Kellogg","orcid":null,"position":3,"is_corresponding":false},{"id":305795,"name":"David R. Linden","orcid":"0000-0002-1727-0387","position":4,"is_corresponding":false},{"id":409812,"name":"Yujiro Hayashi","orcid":"0000-0002-4555-2285","position":5,"is_corresponding":false},{"id":784197,"name":"Vy Truong Thuy Nguyen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:54.209378Z","pmid":"37301443","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":[]}