{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:55:39Z","timestamp":1793382939945,"version":"4.5.0"},"reference-count":189,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U19 AG056278"],"award-info":[{"award-number":["U19 AG056278"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P01 AG043376"],"award-info":[{"award-number":["P01 AG043376"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1 AG063543"],"award-info":[{"award-number":["RO1 AG063543"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P01 AG062413"],"award-info":[{"award-number":["P01 AG062413"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Pittsburgh Medical Center (UPMC)","award":["U19 AG056278"],"award-info":[{"award-number":["U19 AG056278"]}],"id":[{"id":"https:\/\/ror.org\/04ehecz88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Pittsburgh Medical Center (UPMC)","award":["P01 AG043376"],"award-info":[{"award-number":["P01 AG043376"]}],"id":[{"id":"https:\/\/ror.org\/04ehecz88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Pittsburgh Medical Center (UPMC)","award":["RO1 AG063543"],"award-info":[{"award-number":["RO1 AG063543"]}],"id":[{"id":"https:\/\/ror.org\/04ehecz88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Pittsburgh Medical Center (UPMC)","award":["P01 AG062413"],"award-info":[{"award-number":["P01 AG062413"]}],"id":[{"id":"https:\/\/ror.org\/04ehecz88","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Department of Orthopaedic Surgery at UPMC","award":["U19 AG056278"],"award-info":[{"award-number":["U19 AG056278"]}]},{"name":"Department of Orthopaedic Surgery at UPMC","award":["P01 AG043376"],"award-info":[{"award-number":["P01 AG043376"]}]},{"name":"Department of Orthopaedic Surgery at UPMC","award":["RO1 AG063543"],"award-info":[{"award-number":["RO1 AG063543"]}]},{"name":"Department of Orthopaedic Surgery at UPMC","award":["P01 AG062413"],"award-info":[{"award-number":["P01 AG062413"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Closely associated with aging and age-related disorders, cellular senescence (CS) is the inability of cells to proliferate due to accumulated unrepaired cellular damage and irreversible cell cycle arrest. Senescent cells are characterized by their senescence-associated secretory phenotype that overproduces inflammatory and catabolic factors that hamper normal tissue homeostasis. Chronic accumulation of senescent cells is thought to be associated with intervertebral disc degeneration (IDD) in an aging population. This IDD is one of the largest age-dependent chronic disorders, often associated with neurological dysfunctions such as, low back pain, radiculopathy, and myelopathy. Senescent cells (SnCs) increase in number in the aged, degenerated discs, and have a causative role in driving age-related IDD. This review summarizes current evidence supporting the role of CS on onset and progression of age-related IDD. The discussion includes molecular pathways involved in CS such as p53-p21CIP1, p16INK4a, NF-\u03baB, and MAPK, and the potential therapeutic value of targeting these pathways. We propose several mechanisms of CS in IDD including mechanical stress, oxidative stress, genotoxic stress, nutritional deprivation, and inflammatory stress. There are still large knowledge gaps in disc CS research, an understanding of which will provide opportunities to develop therapeutic interventions to treat age-related IDD.<\/jats:p>","DOI":"10.3390\/biom13040686","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:18:13Z","timestamp":1681795093000},"page":"686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":222,"title":["Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8332-024X","authenticated-orcid":false,"given":"Prashanta","family":"Silwal","sequence":"first","affiliation":[{"name":"Ferguson Laboratory for Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Nguyen-Thai","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA"},{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneef Ahamed","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Health Information Management, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Health Information Management, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Institute of the Biology of Aging and Metabolism and Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nam V.","family":"Vo","sequence":"additional","affiliation":[{"name":"Ferguson Laboratory for Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12927","DOI":"10.1111\/acel.12927","article-title":"Systemic clearance of p16(INK4a) -positive senescent cells mitigates age-associated intervertebral disc degeneration","volume":"18","author":"Patil","year":"2019","journal-title":"Aging Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s40610-018-0108-8","article-title":"Cellular senescence in intervertebral disc aging and degeneration","volume":"4","author":"Patil","year":"2018","journal-title":"Curr. 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