{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:18:27Z","timestamp":1788877107792,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR27199517"],"award-info":[{"award-number":["BR27199517"]}]},{"award":["BR27199517"],"award-info":[{"award-number":["BR27199517"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by irreversible extracellular matrix deposition and high mortality, with aging representing its strongest risk factor. Increasing evidence suggests that cellular senescence is not merely a consequence of tissue injury but a central driver of disease progression. Senescent alveolar epithelial cells and fibroblasts contribute to impaired tissue repair and persistent fibrotic remodeling through the acquisition of a senescence-associated secretory phenotype (SASP), which promotes chronic inflammation and amplifies profibrotic signaling. This review provides a comprehensive synthesis of current evidence on the role of cellular senescence in IPF, focusing on key molecular mechanisms, including telomere attrition, mitochondrial dysfunction, oxidative stress, DNA damage response activation, and dysregulated transforming growth factor-\u03b2 (TGF-\u03b2) signaling. A structured literature search was conducted using the PubMed, Scopus, and Web of Science databases to identify mechanistic, translational, and clinical studies related to cellular senescence in IPF. Relevant studies were selected based on conceptual relevance and scientific quality, and findings were qualitatively synthesized within a narrative-review framework. These interconnected pathways form self-reinforcing feedback loops that stabilize the senescent phenotype and sustain fibroblast activation. In addition, we critically evaluate emerging therapeutic strategies targeting senescence, including senolytic and senomorphic approaches, highlighting their potential to modify fundamental disease mechanisms rather than solely attenuating fibrotic progression. Preclinical and early clinical studies suggest that selective targeting of senescent cells may represent a promising avenue for intervention, although challenges related to specificity, safety, and biomarker development remain. Overall, this review positions cellular senescence as a central mechanistic link between aging and fibrosis and underscores its relevance as a translational target in IPF.<\/jats:p>","DOI":"10.3390\/diseases14060201","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:52:30Z","timestamp":1780573950000},"page":"201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cellular Senescence in Idiopathic Pulmonary Fibrosis: Molecular Mechanisms, Pathogenic Networks, and Emerging Therapeutic Targets"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1244-8673","authenticated-orcid":false,"given":"Madina B.","family":"Baurzhan","sequence":"first","affiliation":[{"name":"Research Institute of Balneology and Medical Rehabilitation, Ministry of Health of the Republic of Kazakhstan, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr E.","family":"Gulyayev","sequence":"additional","affiliation":[{"name":"Research Institute of Balneology and Medical Rehabilitation, Ministry of Health of the Republic of Kazakhstan, Astana 010000, Kazakhstan"},{"name":"Laboratory of Drug Discovery and Development, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Joint-Stock Company \u201cKaraganda Medical University\u201d, Karaganda 100008, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6351-6755","authenticated-orcid":false,"given":"Karlygash S.","family":"Absattarova","sequence":"additional","affiliation":[{"name":"Research Institute of Balneology and Medical Rehabilitation, Ministry of Health of the Republic of Kazakhstan, Astana 010000, Kazakhstan"},{"name":"Non-Profit Joint-Stock Company \u00abKazakh National Medical University Named After S.D. Asfendiyarov\u00bb, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayagul A.","family":"Kairgeldina","sequence":"additional","affiliation":[{"name":"Research Institute of Balneology and Medical Rehabilitation, Ministry of Health of the Republic of Kazakhstan, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2452-854X","authenticated-orcid":false,"given":"Kuat","family":"Abzaliyev","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine and Healthcare, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akmaral","family":"Izbassarova","sequence":"additional","affiliation":[{"name":"Non-Profit Joint-Stock Company \u00abKazakh National Medical University Named After S.D. Asfendiyarov\u00bb, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzhan","family":"Lepessova","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kazakh-Russian Medical University, Almaty 050004, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karashash","family":"Absatarova","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics and Evidence-Based Medicine, Faculty of Medicine and Healthcare, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1164\/rccm.202202-0399ST","article-title":"Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: An official ATS\/ERS\/JRS\/ALAT clinical practice guideline","volume":"205","author":"Raghu","year":"2022","journal-title":"Am. 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