{"doi":"10.1016/j.ebiom.2025.105810","title":"Identification of miR-106b-5p as a senolytic miRNA","abstract":"BACKGROUND: Cellular senescence contributes to ageing and age-related diseases. While miR-106b-5p is elevated in centenarians and GH-deficient models of healthy ageing, its role in senescence was unclear. METHODS: Senolytic effects of miR-106b-5p were evaluated in etoposide-induced senescent IMR90 fibroblasts and HUVECs, and in male naturally aged mice using liposome-mediated delivery. Cellular assays, qPCR, Western blotting, and RNA-seq were performed to assess senescence and SASP markers, apoptosis pathways, and molecular mechanisms. FINDINGS: miR-106b-5p selectively eliminated senescent cells without affecting non-senescent cells. It enhanced p53 K120 acetylation and upregulated PUMA, while reducing PCAF expression. In male aged mice, systemic delivery of miR-106b-5p reduced markers of senescence and SASP in multiple tissues and lowered serum IL-6 levels. INTERPRETATION: miR-106b-5p functions as a senolytic miRNA via modulation of the p53-PUMA axis and SASP suppression. It holds promise as a therapeutic agent to mitigate age-related cellular dysfunction and inflammation. FUNDING: Supported by NIH (U19 AG056278, R01 AG063543, P01 AG062413, U54 AG079754, U54 AG076041, R01 AG069819, P01 AI172501), the Glenn Foundation, and NSF grant #2317758.","journal":"EBioMedicine","year":2025,"id":528364,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9678,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":297866,"name":"Allancer Nunes","orcid":"0000-0003-4158-683X","position":1,"is_corresponding":false},{"id":1044901,"name":"Ryan O’Kelly","orcid":null,"position":2,"is_corresponding":false},{"id":234553,"name":"Luise Angelini","orcid":null,"position":3,"is_corresponding":false},{"id":297868,"name":"Michał M. Masternak","orcid":"0000-0002-8483-930X","position":4,"is_corresponding":false},{"id":711446,"name":"Yousin Suh","orcid":"0000-0002-9275-6192","position":5,"is_corresponding":false},{"id":35604,"name":"Xiao Dong","orcid":"0000-0001-9987-5760","position":6,"is_corresponding":false},{"id":233168,"name":"Laura J. Niedernhofer","orcid":"0000-0002-1074-1385","position":7,"is_corresponding":false},{"id":233167,"name":"Paul D. Robbins","orcid":"0000-0003-1068-7099","position":8,"is_corresponding":false},{"id":628293,"name":"Tianpeng Zhang","orcid":"0000-0002-1297-3374","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40554391","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":[]}