{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:39:29Z","timestamp":1790213969913,"version":"4.1.0"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008990","name":"Science and Technology Department of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008990","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008867","name":"Department of Education of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008867","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015258","name":"Zhejiang Provincial People\u2019s Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015258","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Intervertebral disc degeneration (IVDD) refers to the aging and degenerative diseases of intervertebral disc components such as nucleus pulposus, annulus fibrosus, and cartilage endplate, and is the main cause of chronic low back pain. Over the past few years, many researchers around the world concerned that the degeneration of nucleus pulposus (NP) cells plays the main role in IVDD. The degeneration of NP cells is caused by a series of pathological processes, including oxidative stress, inflammatory response, apoptosis, abnormal proliferation, and autophagy. Interestingly, many studies have found a close relationship between the senescence of NP cells and the progression of NP degeneration. The classical aging pathways also have been confirmed to be involved in the pathological process of IVDD. Moreover, several anti-aging drugs have been used to treat IVDD by inhibiting NP cells senescence, such as proanthocyanidins, resveratrol and bone morphogenetic protein 2. Therefore, this article will systematically list and discuss aging, cell senescence, the pathogenesis and targeted therapies of IVDD, in order to provide new ideas for the treatment of IVDD in the future.<\/jats:p>","DOI":"10.3389\/fphar.2023.1172920","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T04:37:46Z","timestamp":1683261466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":68,"title":["Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiongnan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfen","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/ncb2784","article-title":"A complex secretory program orchestrated by the inflammasome controls paracrine senescence","volume":"15","author":"Acosta","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1097\/01.brs.0000231761.73859.2c","article-title":"What is intervertebral disc degeneration, and what causes it?","volume":"31","author":"Adams","year":"2006","journal-title":"Spine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1097\/CORR.0000000000000712","article-title":"Development and characterization of a novel bipedal standing mouse model of intervertebral disc and facet joint degeneration","volume":"477","author":"Ao","year":"2019","journal-title":"Clin. Orthop. Relat. Res."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20190857","article-title":"Higenamine inhibits IL-1\u03b2-induced inflammation in human nucleus pulposus cells","volume":"39","author":"Bai","year":"2019","journal-title":"Biosci. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.matbio.2014.05.005","article-title":"Targeting the extracellular matrix: Matricellular proteins regulate cell\u2013extracellular matrix communication within distinct niches of the intervertebral disc","volume":"37","author":"Bedore","year":"2014","journal-title":"Matrix Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1111\/acel.12592","article-title":"Quantitative identification of senescent cells in aging and disease","volume":"16","author":"Biran","year":"2017","journal-title":"Aging Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"L1124","DOI":"10.1152\/ajplung.00293.2015","article-title":"DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease","volume":"309","author":"Birch","year":"2015","journal-title":"Am. J. Physiology-Lung Cell. Mol. Physiology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"17395","DOI":"10.1074\/jbc.RA119.009167","article-title":"Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion","volume":"294","author":"Blythe","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2166817","DOI":"10.1155\/2022\/2166817","article-title":"The role of oxidative stress in intervertebral disc degeneration","volume":"2022","author":"Cao","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e72489","DOI":"10.1371\/journal.pone.0072489","article-title":"Region specific response of intervertebral disc cells to complex dynamic loading: An organ culture study using a dynamic torsion-compression bioreactor","volume":"8","author":"Chan","year":"2013","journal-title":"PloS one"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1002\/1873-3468.13498","article-title":"Mitochondrial dysfunction and cell senescence: Deciphering a complex relationship","volume":"593","author":"Chapman","year":"2019","journal-title":"FEBS Lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e52570","DOI":"10.7554\/eLife.52570","article-title":"p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle","volume":"9","author":"Che","year":"2020","journal-title":"Elife"},{"key":"B13","doi-asserted-by":"publisher","first-page":"853688","DOI":"10.3389\/fcell.2022.853688","article-title":"Elimination of senescent cells by senolytics facilitates bony endplate microvessel formation and mitigates disc degeneration in aged mice","volume":"10","author":"Chen","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.joca.2020.05.011","article-title":"Melatonin activates autophagy via the NF-\u03baB signaling pathway to prevent extracellular matrix degeneration in intervertebral disc","volume":"28","author":"Chen","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"B15","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1080\/03008207.2022.2063121","article-title":"Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K\/Akt pathway delaying intervertebral disc degeneration","volume":"63","author":"Chen","year":"","journal-title":"Connect. Tissue Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"641098","DOI":"10.3389\/fphar.2021.641098","article-title":"Dehydrocostus lactone attenuates the senescence of nucleus pulposus cells and ameliorates intervertebral disc degeneration via inhibition of STING-TBK1\/NF-\u03baB and MAPK signaling","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"433","DOI":"10.3390\/jcm8040433","article-title":"Curcumin and o-vanillin exhibit evidence of senolytic activity in human IVD cells in vitro","volume":"8","author":"Cherif","year":"2019","journal-title":"J. Clin. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e54693","DOI":"10.7554\/eLife.54693","article-title":"Senotherapeutic drugs for human intervertebral disc degeneration and low back pain","volume":"9","author":"Cherif","year":"2020","journal-title":"Elife"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1038\/nm.4000","article-title":"Cellular senescence in aging and age-related disease: From mechanisms to therapy","volume":"21","author":"Childs","year":"2015","journal-title":"Nat. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1016\/S0140-6736(18)30725-6","article-title":"Low back pain: A major global challenge","volume":"391","author":"Clark","year":"2018","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.jbspin.2009.07.002","article-title":"The intervertebral disc: From pathophysiology to tissue engineering","volume":"76","author":"Clouet","year":"2009","journal-title":"Jt. Bone Spine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.biocel.2007.12.011","article-title":"Pathophysiology of the human intervertebral disc","volume":"40","author":"Colombini","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"29568","DOI":"10.1074\/jbc.M603307200","article-title":"Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence","volume":"281","author":"Copp\u00e9","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/3565127","article-title":"ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases","volume-title":"Oxidative medicine and cellular longevity 2016","author":"Davalli","year":"2016"},{"key":"B25","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: From mechanisms to therapeutic opportunities","volume":"22","author":"Di Micco","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"89","DOI":"10.22203\/ecm.v030a07","article-title":"Oxidative stress inhibits the proliferation, induces premature senescence and promotes a catabolic phenotype in human nucleus pulposus intervertebral disc cells","volume":"30","author":"Dimozi","year":"2015","journal-title":"Eur. Cell Mater"},{"key":"B27","doi-asserted-by":"publisher","first-page":"S46","DOI":"10.1093\/neuros\/nyw078","article-title":"Intervertebral disk degeneration and repair","volume":"80","author":"Dowdell","year":"2017","journal-title":"Neurosurgery"},{"key":"B28","doi-asserted-by":"publisher","first-page":"552","DOI":"10.14336\/AD.2021.1025","article-title":"Cb2r attenuates intervertebral disc degeneration by delaying nucleus pulposus cell senescence through ampk\/gsk3\u03b2 pathway","volume":"13","author":"Du","year":"2022","journal-title":"Aging Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nature02118","article-title":"A DNA damage checkpoint response in telomere-initiated senescence","volume":"426","author":"Fagagna","year":"2003","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1080\/15384101.2016.1152433","article-title":"Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways","volume":"15","author":"Feng","year":"2016","journal-title":"Cell cycle"},{"key":"B31","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/5601593","article-title":"Ros: Crucial intermediators in the pathogenesis of intervertebral disc degeneration","volume-title":"Oxidative medicine and cellular longevity 2017","author":"Feng","year":""},{"key":"B32","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/7426458","article-title":"Oxygen-sensing Nox4 generates genotoxic ROS to induce premature senescence of nucleus pulposus cells through MAPK and NF-\u03baB pathways","volume-title":"Oxidative medicine and cellular longevity 2017","author":"Feng","year":""},{"key":"B33","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm\u2010aging: An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.molmed.2010.03.003","article-title":"Inflammatory networks during cellular senescence: Causes and consequences","volume":"16","author":"Freund","year":"2010","journal-title":"Trends Mol. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.3389\/fphys.2019.01508","article-title":"Are we ill because we age?","volume":"10","author":"Fulop","year":"2019","journal-title":"Front. physiology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.biochi.2021.11.008","article-title":"Role of AMPK mediated pathways in autophagy and aging","volume":"195","author":"Ge","year":"2022","journal-title":"Biochimie"},{"key":"B38","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular senescence: Defining a path forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1016\/S0140-6736(18)30480-X","article-title":"What low back pain is and why we need to pay attention","volume":"391","author":"Hartvigsen","year":"2018","journal-title":"Lancet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1126\/science.1079161","article-title":"Aging and genome maintenance: Lessons from the mouse?","volume":"299","author":"Hasty","year":"2003","journal-title":"Science"},{"key":"B41","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp. Cell Res."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20190112","article-title":"The resistant effect of SIRT1 in oxidative stress-induced senescence of rat nucleus pulposus cell is regulated by Akt-FoxO1 pathway","volume":"39","author":"He","year":"2019","journal-title":"Biosci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1002\/jor.25281","article-title":"Similarity and difference between aging and puncture-induced intervertebral disc degeneration","volume":"40","author":"He","year":"2022","journal-title":"J. Orthop. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1172\/JCI95148","article-title":"Mechanisms and functions of cellular senescence","volume":"128","author":"Herranz","year":"2018","journal-title":"J. Clin. investigation"},{"key":"B45","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/ncb3397","article-title":"NOTCH1 mediates a switch between two distinct secretomes during senescence","volume":"18","author":"Hoare","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.berh.2009.11.002","article-title":"Measuring the global burden of low back pain","volume":"24","author":"Hoy","year":"2010","journal-title":"Best Pract. Res. Clin. rheumatology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"11732","DOI":"10.18632\/aging.103339","article-title":"Chemerin facilitates intervertebral disc degeneration via TLR4 and CMKLR1 and activation of NF-kB signaling pathway","volume":"12","author":"Hu","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"13849","DOI":"10.1080\/21655979.2022.2084495","article-title":"Omentin-1 alleviate interleukin-1\u03b2(IL-1\u03b2)-induced nucleus pulposus cells senescence","volume":"13","author":"Huang","year":"","journal-title":"Bioengineered"},{"key":"B49","doi-asserted-by":"publisher","first-page":"837777","DOI":"10.3389\/fcell.2021.837777","article-title":"Cationic polymer brush-modified carbon nanotube-meditated eRNA LINC02569 silencing attenuates nucleus pulposus degeneration by blocking NF-\u03baB signaling pathway and alleviate cell senescence","volume":"9","author":"Huang","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"932","DOI":"10.18632\/aging.100520","article-title":"IL1-and TGF\u03b2-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine \u2018bystander senescence","volume":"4","author":"Hubackova","year":"2012","journal-title":"Aging (Albany NY)"},{"key":"B51","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1038\/nm.4324","article-title":"Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment","volume":"23","author":"Jeon","year":"2017","journal-title":"Nat. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.spinee.2013.06.099","article-title":"In vitro lifespan and senescence mechanisms of human nucleus pulposus chondrocytes","volume":"14","author":"Jeong","year":"2014","journal-title":"Spine J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e12779","DOI":"10.1111\/cpr.12779","article-title":"The mitochondria\u2010targeted anti\u2010oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance","volume":"53","author":"Kang","year":"2020","journal-title":"Cell Prolif."},{"key":"B54","doi-asserted-by":"publisher","first-page":"7810320","DOI":"10.1155\/2019\/7810320","article-title":"Restoration of autophagic flux rescues oxidative damage and mitochondrial dysfunction to protect against intervertebral disc degeneration","volume":"2019","author":"Kang","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"B55","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.cell.2014.10.039","article-title":"Geroscience: Linking aging to chronic disease","volume":"159","author":"Kennedy","year":"2014","journal-title":"Cell"},{"key":"B56","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.spinee.2009.04.018","article-title":"Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs","volume":"9","author":"Kim","year":"2009","journal-title":"Spine J."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e13270","DOI":"10.1111\/acel.13270","article-title":"On the evolution of cellular senescence","volume":"19","author":"Kowald","year":"2020","journal-title":"Aging Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"12072","DOI":"10.1073\/pnas.211053698","article-title":"Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging","volume":"98","author":"Krtolica","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"R732","DOI":"10.1186\/ar1732","article-title":"The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration","volume":"7","author":"Le Maitre","year":"2005","journal-title":"Arthritis Res. Ther."},{"key":"B60","doi-asserted-by":"publisher","first-page":"R77","DOI":"10.1186\/ar2275","article-title":"Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile","volume":"9","author":"Le Maitre","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20190126","article-title":"Resveratrol attenuates inflammation environment-induced nucleus pulposus cell senescence in vitro","volume":"39","author":"Li","year":"2019","journal-title":"Biosci. Rep."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1002\/jcp.29097","article-title":"TIGAR impedes compression\u2010induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy","volume":"235","author":"Li","year":"2020","journal-title":"J. Cell. physiology"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.21037\/atm-21-4876","article-title":"The monocyte to high-density lipoprotein cholesterol ratio and outcomes in type 2 diabetes mellitus patients with non-ST-segment elevation acute coronary syndrome","volume":"9","author":"Liang","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1073\/pnas.1818313116","article-title":"Cells exhibiting strong p16 INK4a promoter activation in vivo display features of senescence","volume":"116","author":"Liu","year":"2019","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3141","DOI":"10.1111\/os.13560","article-title":"Pharmacological effects of resveratrol in intervertebral disc degeneration: A literature review","volume":"14","author":"Liu","year":"2022","journal-title":"Orthop. Surg."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"5231","DOI":"10.26355\/eurrev_202005_21305","article-title":"Matrilin-3 alleviates extracellular matrix degradation of nucleus pulposus cells via induction of IL-1 receptor antagonist","volume":"24","author":"Lu","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/S0140-6736(16)30970-9","article-title":"Non-specific low back pain","volume":"389","author":"Maher","year":"2017","journal-title":"Lancet"},{"key":"B69","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.exger.2016.05.010","article-title":"Keeping the senescence secretome under control: Molecular reins on the senescence-associated secretory phenotype","volume":"82","author":"Malaquin","year":"2016","journal-title":"Exp. Gerontol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13075-021-02504-z","article-title":"Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin","volume":"23","author":"Mannarino","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"B71","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1097\/00007632-198802000-00008","article-title":"Lumbar disc degeneration: Correlation with age, sex, and spine level in 600 autopsy specimens","volume":"13","author":"Miller","year":"1988","journal-title":"Spine"},{"key":"B72","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/ar630","article-title":"Aggrecanases and cartilage matrix degradation","volume":"5","author":"Nagase","year":"2003","journal-title":"Arthritis Res. Ther."},{"key":"B73","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.mad.2012.11.002","article-title":"Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs","volume":"134","author":"Nasto","year":"2013","journal-title":"Mech. ageing Dev."},{"key":"B74","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/j.1474-9726.2012.00795.x","article-title":"A senescent cell bystander effect: Senescence\u2010induced senescence","volume":"11","author":"Nelson","year":"2012","journal-title":"Aging Cell"},{"key":"B75","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.matbio.2019.02.004","article-title":"p16Ink4a deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence","volume":"82","author":"Novais","year":"2019","journal-title":"Matrix Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.1038\/s41467-021-25453-2","article-title":"Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice","volume":"12","author":"Novais","year":"2021","journal-title":"Nat. Commun."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1016\/j.spinee.2013.07.490","article-title":"Pathomechanisms of discogenic low back pain in humans and animal models","volume":"15","author":"Ohtori","year":"2015","journal-title":"spine J."},{"key":"B78","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/bs.ircmb.2016.04.003","article-title":"NF-\u03baB signaling as a driver of ageing","volume":"326","author":"Osorio","year":"2016","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1182\/blood-2017-07-746396","article-title":"DNA damage responses and p53 in the aging process","volume":"131","author":"Ou","year":"2018","journal-title":"Blood, J. Am. Soc. Hematol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"e12927","DOI":"10.1111\/acel.12927","article-title":"Systemic clearance of p16INK4a\u2010positive senescent cells mitigates age\u2010associated intervertebral disc degeneration","volume":"18","author":"Patil","year":"","journal-title":"Aging Cell"},{"key":"B81","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.mad.2019.04.006","article-title":"Oxidative stress-induced senescence markedly increases disc cell bioenergetics","volume":"180","author":"Patil","year":"","journal-title":"Mech. ageing Dev."},{"key":"B82","doi-asserted-by":"publisher","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. Mol. Biol. Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1111\/j.1469-7580.2012.01521.x","article-title":"Diversity of intervertebral disc cells: Phenotype and function","volume":"221","author":"Pattappa","year":"2012","journal-title":"J. Anat."},{"key":"B84","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.bbrc.2013.02.034","article-title":"A role for TNF\u03b1 in intervertebral disc degeneration: A non-recoverable catabolic shift","volume":"433","author":"Purmessur","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B85","doi-asserted-by":"publisher","first-page":"12645","DOI":"10.26355\/eurrev_202012_24161","article-title":"Inhibition of p53\/p21 by TWIST alleviates TNF-\u03b1 induced nucleus pulposus cell senescence in vitro","volume":"24","author":"Qiu","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B86","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12967-019-1886-3","article-title":"RIPK1 suppresses apoptosis mediated by TNF and caspase-3 in intervertebral discs","volume":"17","author":"Qiu","year":"2019","journal-title":"J. Transl. Med."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1002\/ijc.27316","article-title":"Cellular senescence and tumor suppressor gene p16","volume":"130","author":"Rayess","year":"2012","journal-title":"Int. J. cancer"},{"key":"B88","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","article-title":"Role of cytokines in intervertebral disc degeneration: Pain and disc content","volume":"10","author":"Risbud","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/ncb1909","article-title":"Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion","volume":"11","author":"Rodier","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"e1033","DOI":"10.1002\/jsp2.1033","article-title":"Osteoarthritis and intervertebral disc degeneration: Quite different, quite similar","volume":"1","author":"Rustenburg","year":"2018","journal-title":"JOR spine"},{"key":"B91","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s11357-021-00341-1","article-title":"Targeting mitochondrial dysfunction with small molecules in intervertebral disc aging and degeneration","volume":"43","author":"Saberi","year":"2021","journal-title":"Geroscience"},{"key":"B92","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41434-018-0004-0","article-title":"Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: A review","volume":"25","author":"Sampara","year":"2018","journal-title":"Gene Ther."},{"key":"B93","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.joca.2020.11.006","article-title":"Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2\/NF-\u03baB axis","volume":"29","author":"Shao","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"B94","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/medsci6020034","article-title":"The role of adipokines in intervertebral disc degeneration","volume":"6","author":"Sharma","year":"2018","journal-title":"Med. Sci."},{"key":"B95","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/s0960-9822(99)80420-5","article-title":"Microarray analysis of replicative senescence","volume":"9","author":"Shelton","year":"1999","journal-title":"Curr. Biol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13075-022-02804-y","article-title":"Excessive mechanical stress-induced intervertebral disc degeneration is related to Piezo1 overexpression triggering the imbalance of autophagy\/apoptosis in human nucleus pulpous","volume":"24","author":"Shi","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"B97","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.redox.2018.09.006","article-title":"Sirtuin 3-dependent mitochondrial redox homeostasis protects against AGEs-induced intervertebral disc degeneration","volume":"19","author":"Song","year":"2018","journal-title":"Redox Biol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1097\/BRS.0b013e31817e2ce3","article-title":"Characterization of intervertebral disc aging: Longitudinal analysis of a rabbit model by magnetic resonance imaging, histology, and gene expression","volume":"33","author":"Sowa","year":"2008","journal-title":"Spine"},{"key":"B99","doi-asserted-by":"publisher","first-page":"2774","DOI":"10.3390\/ijms20112774","article-title":"mTOR and aging: an old fashioned dress","volume":"20","author":"Stallone","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"6612","DOI":"10.3390\/ijms23126612","article-title":"Current perspectives on nucleus pulposus fibrosis in disc degeneration and repair","volume":"23","author":"Sun","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B101","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.omtn.2021.02.009","article-title":"MicroRNA-199a-5p accelerates nucleus pulposus cell apoptosis and IVDD by inhibiting SIRT1-mediated deacetylation of p21","volume":"24","author":"Sun","year":"2021","journal-title":"Mol. Therapy-Nucleic Acids"},{"key":"B102","doi-asserted-by":"publisher","first-page":"583","DOI":"10.3892\/ijmm.2018.3972","article-title":"Bone morphogenetic protein 2 alleviated intervertebral disc degeneration through mediating the degradation of ECM and apoptosis of nucleus pulposus cells via the PI3K\/Akt pathway","volume":"43","author":"Tan","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"B103","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.molmed.2017.02.005","article-title":"Mitochondrial sirtuins and molecular mechanisms of aging","volume":"23","author":"Van de Ven","year":"2017","journal-title":"Trends Mol. Med."},{"key":"B104","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nature13193","article-title":"The role of senescent cells in ageing","volume":"509","author":"Van Deursen","year":"2014","journal-title":"Nature"},{"key":"B105","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.joca.2015.03.028","article-title":"Mechanics and biology in intervertebral disc degeneration: A vicious circle","volume":"23","author":"Vergroesen","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"B106","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/nature19329","article-title":"Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice","volume":"537","author":"Vermeij","year":"2016","journal-title":"Nature"},{"key":"B107","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/jor.22204","article-title":"An overview of underlying causes and animal models for the study of age\u2010related degenerative disorders of the spine and synovial joints","volume":"31","author":"Vo","year":"2013","journal-title":"J. Orthop. Res."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/jor.21153","article-title":"Accelerated aging of intervertebral discs in a mouse model of progeria","volume":"28","author":"Vo","year":"2010","journal-title":"J. Orthop. Res."},{"key":"B109","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1002\/jor.23195","article-title":"Molecular mechanisms of biological aging in intervertebral discs","volume":"34","author":"Vo","year":"2016","journal-title":"J. Orthop. Res."},{"key":"B110","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: A systematic analysis for the global burden of disease study 2013","volume":"386","author":"Vos","year":"2015","journal-title":"lancet"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.joca.2011.04.005","article-title":"Complex loading affects intervertebral disc mechanics and biology","volume":"19","author":"Walter","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"B112","doi-asserted-by":"publisher","first-page":"613006","DOI":"10.3389\/fcell.2020.613006","article-title":"Quercetin suppresses apoptosis and attenuates intervertebral disc degeneration via the SIRT1-autophagy pathway","volume":"8","author":"Wang","year":"","journal-title":"Front. Cell Dev. Biol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.joca.2012.04.010","article-title":"Spine degeneration in a murine model of chronic human tobacco smokers","volume":"20","author":"Wang","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"B114","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.joca.2015.09.019","article-title":"Aging and age related stresses: A senescence mechanism of intervertebral disc degeneration","volume":"24","author":"Wang","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"B115","doi-asserted-by":"publisher","first-page":"5720","DOI":"10.1111\/jcmm.13848","article-title":"Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats","volume":"22","author":"Wang","year":"","journal-title":"J. Cell Mol. Med."},{"key":"B116","doi-asserted-by":"publisher","first-page":"e923386","DOI":"10.12659\/MSM.923386","article-title":"Dioscin attenuates interleukin 1\u03b2 (IL-1\u03b2)-induced catabolism and apoptosis via modulating the toll-like receptor 4 (Tlr4)\/nuclear factor kappa B (NF-\u03baB) signaling in human nucleus pulposus cells","volume":"26","author":"Wang","year":"","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"B117","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.cca.2015.06.023","article-title":"MMPs and ADAMTSs in intervertebral disc degeneration","volume":"448","author":"Wang","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"B118","doi-asserted-by":"publisher","first-page":"6192498","DOI":"10.1155\/2021\/6192498","article-title":"Deficiency of MIF accentuates overloaded compression-induced nucleus pulposus cell oxidative damage via depressing mitophagy","volume":"2021","author":"Wang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B119","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.bbrc.2018.06.031","article-title":"PINK1 protects against oxidative stress induced senescence of human nucleus pulposus cells via regulating mitophagy","volume":"504","author":"Wang","year":"","journal-title":"Biochem. biophysical Res. Commun."},{"key":"B120","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.mad.2005.09.005","article-title":"Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16\/FOXO","volume":"127","author":"Wang","year":"2006","journal-title":"Mech. ageing Dev."},{"key":"B121","doi-asserted-by":"publisher","first-page":"7961","DOI":"10.18632\/aging.102302","article-title":"Kinsenoside ameliorates intervertebral disc degeneration through the activation of AKT-ERK1\/2-Nrf2 signaling pathway","volume":"11","author":"Wang","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"B122","doi-asserted-by":"publisher","first-page":"1052878","DOI":"10.3389\/fmolb.2022.1052878","article-title":"The role of ageing and oxidative stress in intervertebral disc degeneration","volume":"9","author":"Wen","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"B123","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.cmet.2015.11.011","article-title":"Mitochondrial dysfunction induces senescence with a distinct secretory phenotype","volume":"23","author":"Wiley","year":"2016","journal-title":"Cell metab."},{"key":"B124","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1016\/j.ymthe.2022.05.021","article-title":"Self-amplifying loop of NF-\u03baB and periostin initiated by PIEZO1 accelerates mechano-induced senescence of nucleus pulposus cells and intervertebral disc degeneration","volume":"30","author":"Wu","year":"","journal-title":"Mol. Ther."},{"key":"B125","doi-asserted-by":"publisher","first-page":"823945","DOI":"10.3389\/fbioe.2022.823945","article-title":"Senolytics: Eliminating senescent cells and alleviating intervertebral disc degeneration","volume":"10","author":"Wu","year":"","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1055\/s-0033-1347299","article-title":"Inflammatory mediators in intervertebral disk degeneration and discogenic pain","volume":"3","author":"Wuertz","year":"2013","journal-title":"Glob. spine J."},{"key":"B127","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1002\/cbin.11258","article-title":"PTEN promotes intervertebral disc degeneration by regulating nucleus pulposus cell behaviors","volume":"44","author":"Xi","year":"2020","journal-title":"Cell Biol. Int."},{"key":"B128","doi-asserted-by":"publisher","first-page":"787278","DOI":"10.3389\/fcell.2021.787278","article-title":"Apigenin alleviates intervertebral disc degeneration via restoring autophagy flux in nucleus pulposus cells","volume":"9","author":"Xie","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B129","doi-asserted-by":"crossref","DOI":"10.1111\/os.13254","volume-title":"Treatment of intervertebral disc degeneration","author":"Xin","year":"2022"},{"key":"B130","doi-asserted-by":"publisher","first-page":"E1253","DOI":"10.1097\/BRS.0b013e3181e7d087","article-title":"Leg amputation accelerates senescence of rat lumbar intervertebral discs","volume":"35","author":"Xing","year":"2010","journal-title":"Spine"},{"key":"B131","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.7150\/thno.30658","article-title":"Progerin accumulation in nucleus pulposus cells impairs mitochondrial function and induces intervertebral disc degeneration and therapeutic effects of sulforaphane","volume":"9","author":"Xu","year":"2019","journal-title":"Theranostics"},{"key":"B132","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1002\/jcb.27683","article-title":"Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA-Piezo1 under abnormal mechanical stretch stress","volume":"120","author":"Yang","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B133","doi-asserted-by":"publisher","first-page":"e62852","DOI":"10.7554\/eLife.62852","article-title":"DNA damage\u2014How and why we age?","volume":"10","author":"Yousefzadeh","year":"2021","journal-title":"Elife"},{"key":"B134","doi-asserted-by":"publisher","first-page":"e1082","DOI":"10.1002\/jsp2.1082","article-title":"Autophagy and mTOR signaling during intervertebral disc aging and degeneration","volume":"3","author":"Yurube","year":"2020","journal-title":"JOR spine"},{"key":"B135","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1007\/s00586-005-0957-8","article-title":"Significance of the mechanical environment during regeneration of the intervertebral disc","volume":"14","author":"Zeiter","year":"2005","journal-title":"Eur. Spine J."},{"key":"B136","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1089\/dna.2021.1012","article-title":"Update on the correlation between mitochondrial dysfunction and intervertebral disk degeneration","volume":"41","author":"Zhang","year":"2022","journal-title":"DNA Cell Biol."},{"key":"B137","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.cca.2020.04.016","article-title":"Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function","volume":"508","author":"Zhang","year":"2020","journal-title":"Clin. Chim. acta"},{"key":"B138","doi-asserted-by":"publisher","first-page":"e13057","DOI":"10.1111\/cpr.13057","article-title":"NF\u2010\u03baB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration","volume":"54","author":"Zhang","year":"","journal-title":"Cell Prolif."},{"key":"B139","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1002\/cbin.11650","article-title":"Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2","volume":"45","author":"Zhang","year":"","journal-title":"Cell Biol. Int."},{"key":"B140","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.joca.2020.09.002","article-title":"The role of structure and function changes of sensory nervous system in intervertebral disc-related low back pain","volume":"29","author":"Zhang","year":"","journal-title":"Osteoarthr. Cartil."},{"key":"B141","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1007\/s11010-021-04052-1","article-title":"Activation of HSP70 impedes tert-butyl hydroperoxide (t-BHP)-induced apoptosis and senescence of human nucleus pulposus stem cells via inhibiting the JNK\/c-Jun pathway","volume":"476","author":"Zhang","year":"","journal-title":"Mol. Cell Biochem."},{"key":"B142","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/7959573","article-title":"The Sirt1\/P53 axis in diabetic intervertebral disc degeneration pathogenesis and therapeutics","volume-title":"Oxidative medicine and cellular longevity 2019","author":"Zhang","year":"2019"},{"key":"B143","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.arr.2007.08.001","article-title":"The cell biology of intervertebral disc aging and degeneration","volume":"6","author":"Zhao","year":"2007","journal-title":"Ageing Res. Rev."},{"key":"B144","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nature25743","article-title":"Structure and mechanogating mechanism of the Piezo1 channel","volume":"554","author":"Zhao","year":"2018","journal-title":"Nature"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1172920\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T04:37:56Z","timestamp":1683261476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1172920\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":144,"alternative-id":["10.3389\/fphar.2023.1172920"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1172920","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]},"article-number":"1172920"}}