{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:03:03Z","timestamp":1789401783847,"version":"build-2803163510"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404113"],"award-info":[{"award-number":["82404113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402802"],"award-info":[{"award-number":["82402802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M742390"],"award-info":[{"award-number":["2023M742390"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515111068"],"award-info":[{"award-number":["2023A1515111068"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20230807095121041"],"award-info":[{"award-number":["JCYJ20230807095121041"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20230807095203007"],"award-info":[{"award-number":["JCYJ20230807095203007"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["RCBS20231211090537061"],"award-info":[{"award-number":["RCBS20231211090537061"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["SZXK023"],"award-info":[{"award-number":["SZXK023"]}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202211038"],"award-info":[{"award-number":["SZSM202211038"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen High-level Hospital Construction Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Accumulating evidence has suggested that intervertebral disc degeneration (IVDD) serves as a health problem deserving attention from worldwide, owing to the low back pain and even disability it causes. Cellular senescence, an irreversible process of terminal cell cycle arrest, plays an essential role in the degeneration of nucleus pulposus (NP) cells and IVDD with an unknown underlying mechanism. Here, we have explored the senescence signature in IVDD through high dimensional weighted gene co-expression network analysis (hdWGCNA) algorithm in two single cell datasets (PRJCA014236 and GSE244889) to construct a novel signature called NP_Senescence, which accurately identifies the patients with IVDD. The efficacy and accuracy were validated in various external datasets, including two expression array datasets (GSE70362 and GSE34095) and one single cell dataset (GSE230809). Additionally, the accuracy of the specific model was also verified with the senescent cell identification (SenCID) algorithm. IVDD patients with a high NP_Senescence score exhibited the characteristics of compensated activation of hyaluronic acid monomers synthesis and abnormal status of DNA damage repair through single-cell Flux Estimation Analysis (scFEA) algorithm. Furthermore, the NP_Senescence was negatively associated with the level of AMP and Glucose-1-phosphate, while positively associated with the level of \u03b2-alanine and UDP-glucuronic acid. In conclusion, we constructed a novel disc-specific scoring model NP_Senescence by comprehensively analyzing the senescence-related genes of IVDD, which can be used for patient early diagnosis and treatment, as well as the identification of metabolic characteristics.<\/jats:p>","DOI":"10.1007\/s11357-025-01962-6","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T21:43:32Z","timestamp":1762983812000},"page":"5875-5893","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An integrated multi-algorithm analysis to decipher senescence and metabolic characteristics in nucleus pulposus cells during disc degeneration"],"prefix":"10.1007","volume":"48","author":[{"given":"Zhuangyao","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuluan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"1962_CR1","doi-asserted-by":"publisher","unstructured":"Collaborators, G. B. D. L. B. P. Global, regional, and national burden of low back pain, 1990-2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5, e316-e329. https:\/\/doi.org\/10.1016\/S2665-9913(23)00098-X","DOI":"10.1016\/S2665-9913(23)00098-X"},{"key":"1962_CR2","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1016\/S0140-6736(18)30480-X","volume":"391","author":"J Hartvigsen","year":"2018","unstructured":"Hartvigsen J, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391:2356\u201367. https:\/\/doi.org\/10.1016\/S0140-6736(18)30480-X.","journal-title":"Lancet"},{"key":"1962_CR3","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","volume":"28","author":"A Hernandez-Segura","year":"2018","unstructured":"Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28:436\u201353. https:\/\/doi.org\/10.1016\/j.tcb.2018.02.001.","journal-title":"Trends Cell Biol"},{"issue":"Suppl 3","key":"1962_CR4","doi-asserted-by":"publisher","first-page":"S312","DOI":"10.1007\/s00586-006-0126-8","volume":"15","author":"S Roberts","year":"2006","unstructured":"Roberts S, Evans EH, Kletsas D, Jaffray DC, Eisenstein SM. Senescence in human intervertebral discs. Eur Spine J. 2006;15(Suppl 3):S312-316. https:\/\/doi.org\/10.1007\/s00586-006-0126-8.","journal-title":"Eur Spine J"},{"key":"1962_CR5","doi-asserted-by":"publisher","first-page":"e21795","DOI":"10.1096\/fj.202002201R","volume":"35","author":"S Ashraf","year":"2021","unstructured":"Ashraf S, Santerre P, Kandel R. Induced senescence of healthy nucleus pulposus cells is mediated by paracrine signaling from TNF-alpha-activated cells. FASEB J. 2021;35:e21795. https:\/\/doi.org\/10.1096\/fj.202002201R.","journal-title":"FASEB J"},{"key":"1962_CR6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","volume":"10","author":"MV Risbud","year":"2014","unstructured":"Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol. 2014;10:44\u201356. https:\/\/doi.org\/10.1038\/nrrheum.2013.160.","journal-title":"Nat Rev Rheumatol"},{"key":"1962_CR7","doi-asserted-by":"publisher","first-page":"e2411162","DOI":"10.1002\/advs.202411162","volume":"12","author":"H Gu","year":"2025","unstructured":"Gu H, et al. SPP1-ITGalpha5\/beta1 accelerates calcification of nucleus pulposus cells by inhibiting mitophagy via ubiquitin-dependent PINK1\/PARKIN pathway blockade. Adv Sci (Weinh). 2025;12:e2411162. https:\/\/doi.org\/10.1002\/advs.202411162.","journal-title":"Adv Sci (Weinh)"},{"key":"1962_CR8","doi-asserted-by":"publisher","first-page":"111277","DOI":"10.1016\/j.cellsig.2024.111277","volume":"121","author":"D Zhu","year":"2024","unstructured":"Zhu D, et al. POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt\/beta-catenin and NF-kappaB signal pathway in intervertebral disc degeneration. Cell Signal. 2024;121:111277. https:\/\/doi.org\/10.1016\/j.cellsig.2024.111277.","journal-title":"Cell Signal"},{"key":"1962_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00373-1","volume":"12","author":"O Wu","year":"2024","unstructured":"Wu O, et al. KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m(6)A modification of ATG4a to promote NPCs senescence and IVDD progression. Bone Res. 2024;12:67. https:\/\/doi.org\/10.1038\/s41413-024-00373-1.","journal-title":"Bone Res"},{"key":"1962_CR10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.freeradbiomed.2024.08.015","volume":"224","author":"ZL Wu","year":"2024","unstructured":"Wu ZL, et al. Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration. Free Radic Biol Med. 2024;224:9\u201322. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2024.08.015.","journal-title":"Free Radic Biol Med"},{"key":"1962_CR11","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8040433","author":"H Cherif","year":"2019","unstructured":"Cherif H, et al. Curcumin and o-vanillin exhibit evidence of senolytic activity in human IVD cells in vitro. J Clin Med. 2019. https:\/\/doi.org\/10.3390\/jcm8040433.","journal-title":"J Clin Med"},{"key":"1962_CR12","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.joca.2020.11.006","volume":"29","author":"Z Shao","year":"2021","unstructured":"Shao Z, et al. Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2\/NF-kappaB axis. Osteoarthritis Cartilage. 2021;29:413\u201322. https:\/\/doi.org\/10.1016\/j.joca.2020.11.006.","journal-title":"Osteoarthritis Cartilage"},{"key":"1962_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1439976","volume":"15","author":"M Wang","year":"2024","unstructured":"Wang M, et al. Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration. Front Immunol. 2024;15:1439976. https:\/\/doi.org\/10.3389\/fimmu.2024.1439976.","journal-title":"Front Immunol"},{"key":"1962_CR14","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.70072","volume":"12","author":"Z Zhao","year":"2024","unstructured":"Zhao Z, et al. Senescence in intervertebral disc degeneration: a comprehensive analysis based on bioinformatic strategies. Immunity, Inflammation and Disease. 2024;12:e70072. https:\/\/doi.org\/10.1002\/iid3.70072.","journal-title":"Immunity, Inflammation and Disease"},{"key":"1962_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00646-9","volume":"6","author":"X Zhu","year":"2021","unstructured":"Zhu X, et al. Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention. Signal Transduct Target Ther. 2021;6:245. https:\/\/doi.org\/10.1038\/s41392-021-00646-9.","journal-title":"Signal Transduct Target Ther"},{"key":"1962_CR16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1146\/annurev-biochem-062917-012239","volume":"87","author":"LJ Niedernhofer","year":"2018","unstructured":"Niedernhofer LJ, et al. Nuclear genomic instability and aging. Annu Rev Biochem. 2018;87:295\u2013322. https:\/\/doi.org\/10.1146\/annurev-biochem-062917-012239.","journal-title":"Annu Rev Biochem"},{"key":"1962_CR17","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.cmet.2014.10.008","volume":"20","author":"I Shimizu","year":"2014","unstructured":"Shimizu I, Yoshida Y, Suda M, Minamino T. DNA damage response and metabolic disease. Cell Metab. 2014;20:967\u201377. https:\/\/doi.org\/10.1016\/j.cmet.2014.10.008.","journal-title":"Cell Metab"},{"key":"1962_CR18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cmet.2016.09.017","volume":"25","author":"TES Kauppila","year":"2017","unstructured":"Kauppila TES, Kauppila JHK, Larsson NG. Mammalian mitochondria and aging: an update. Cell Metab. 2017;25:57\u201371. https:\/\/doi.org\/10.1016\/j.cmet.2016.09.017.","journal-title":"Cell Metab"},{"key":"1962_CR19","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1101\/gr.271205.120","volume":"31","author":"N Alghamdi","year":"2021","unstructured":"Alghamdi N, et al. A graph neural network model to estimate cell-wise metabolic flux using single-cell RNA-seq data. Genome Res. 2021;31:1867\u201384. https:\/\/doi.org\/10.1101\/gr.271205.120.","journal-title":"Genome Res"},{"key":"1962_CR20","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1038\/s41588-021-00894-z","volume":"53","author":"S Morabito","year":"2021","unstructured":"Morabito S, et al. Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer\u2019s disease. Nat Genet. 2021;53:1143\u201355. https:\/\/doi.org\/10.1038\/s41588-021-00894-z.","journal-title":"Nat Genet"},{"key":"1962_CR21","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36:411\u201320. https:\/\/doi.org\/10.1038\/nbt.4096.","journal-title":"Nat Biotechnol"},{"key":"1962_CR22","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","volume":"16","author":"I Korsunsky","year":"2019","unstructured":"Korsunsky I, et al. Fast, sensitive and accurate integration of single-cell data with harmony. Nat Methods. 2019;16:1289\u201396. https:\/\/doi.org\/10.1038\/s41592-019-0619-0.","journal-title":"Nat Methods"},{"key":"1962_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106692","volume":"26","author":"D Wang","year":"2023","unstructured":"Wang D, et al. Single-cell transcriptomics reveals heterogeneity and intercellular crosstalk in human intervertebral disc degeneration. iScience. 2023;26:106692. https:\/\/doi.org\/10.1016\/j.isci.2023.106692.","journal-title":"iScience"},{"issue":"5","key":"1962_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.03.009","volume":"36","author":"W Tao","year":"2024","unstructured":"Tao W, Yu Z, Han JJ. Single-cell senescence identification reveals senescence heterogeneity, trajectory, and modulators. Cell Metab. 2024;36(5):1126\u20131143. https:\/\/doi.org\/10.1016\/j.cmet.2024.03.009.","journal-title":"Cell Metab"},{"key":"1962_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu T, et al. Clusterprofiler 4.0: a universal enrichment tool for interpreting omics data. Innov (Camb). 2021;2:100141. https:\/\/doi.org\/10.1016\/j.xinn.2021.100141.","journal-title":"Innov (Camb)"},{"key":"1962_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-023-00485-5","volume":"10","author":"ZQ Wen","year":"2023","unstructured":"Wen ZQ, et al. Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases. Mil Med Res. 2023;10:54. https:\/\/doi.org\/10.1186\/s40779-023-00485-5.","journal-title":"Mil Med Res"},{"key":"1962_CR27","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.177789","author":"B Zheng","year":"2024","unstructured":"Zheng B, et al. S1P regulates intervertebral disc aging by mediating endoplasmic reticulum-mitochondrial calcium ion homeostasis. JCI Insight. 2024. https:\/\/doi.org\/10.1172\/jci.insight.177789.","journal-title":"JCI Insight"},{"key":"1962_CR28","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.joca.2023.01.006","volume":"31","author":"S Li","year":"2023","unstructured":"Li S, et al. IL-37 alleviates intervertebral disc degeneration via the IL-1R8\/NF-kappaB pathway. Osteoarthritis Cartilage. 2023;31:588\u201399. https:\/\/doi.org\/10.1016\/j.joca.2023.01.006.","journal-title":"Osteoarthritis Cartilage"},{"key":"1962_CR29","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3171\/spi.2003.98.1.0063","volume":"98","author":"S Matsunaga","year":"2003","unstructured":"Matsunaga S, et al. Age-related changes in expression of transforming growth factor-\u03b2 and receptors in cells of intervertebral discs. J Neurosurg. 2003;98:63\u20137. https:\/\/doi.org\/10.3171\/spi.2003.98.1.0063.","journal-title":"J Neurosurg"},{"key":"1962_CR30","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.jot.2024.08.022","volume":"49","author":"P Xue","year":"2024","unstructured":"Xue P, et al. Unveiling the role of CXCL8\/CXCR2 in intervertebral disc degeneration: a path to promising therapeutic strategies. J Orthop Transl. 2024;49:119\u201334. https:\/\/doi.org\/10.1016\/j.jot.2024.08.022.","journal-title":"J Orthop Transl"},{"key":"1962_CR31","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.matbio.2019.02.004","volume":"82","author":"EJ Novais","year":"2019","unstructured":"Novais EJ, Diekman BO, Shapiro IM, Risbud MV. P16(Ink4a) deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence. Matrix Biol. 2019;82:54\u201370. https:\/\/doi.org\/10.1016\/j.matbio.2019.02.004.","journal-title":"Matrix Biol"},{"key":"1962_CR32","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.7150\/thno.30658","volume":"9","author":"X Xu","year":"2019","unstructured":"Xu X, et al. Progerin accumulation in nucleus pulposus cells impairs mitochondrial function and induces intervertebral disc degeneration and therapeutic effects of sulforaphane. Theranostics. 2019;9:2252\u201367. https:\/\/doi.org\/10.7150\/thno.30658.","journal-title":"Theranostics"},{"key":"1962_CR33","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202404275","volume":"11","author":"Y Jin","year":"2024","unstructured":"Jin Y, et al. Hypoxia-preconditioned BMSC-derived exosomes induce mitophagy via the BNIP3-ANAX2 axis to alleviate intervertebral disc degeneration. Adv Sci. 2024;11:e2404275. https:\/\/doi.org\/10.1002\/advs.202404275.","journal-title":"Adv Sci"},{"key":"1962_CR34","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","volume":"179","author":"V Gorgoulis","year":"2019","unstructured":"Gorgoulis V, et al. Cellular senescence: defining a path forward. Cell. 2019;179:813\u201327. https:\/\/doi.org\/10.1016\/j.cell.2019.10.005.","journal-title":"Cell"},{"key":"1962_CR35","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1093\/toxsci\/kft111","volume":"134","author":"L Gu","year":"2013","unstructured":"Gu L, et al. Intervention in genotoxic stress-induced senescence by cordycepin through activation of eIF2alpha and suppression of Sp1. Toxicol Sci. 2013;134:345\u201354. https:\/\/doi.org\/10.1093\/toxsci\/kft111.","journal-title":"Toxicol Sci"},{"key":"1962_CR36","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1002\/jor.23195","volume":"34","author":"NV Vo","year":"2016","unstructured":"Vo NV, et al. Molecular mechanisms of biological aging in intervertebral discs. J Orthop Res. 2016;34:1289\u2013306. https:\/\/doi.org\/10.1002\/jor.23195.","journal-title":"J Orthop Res"},{"key":"1962_CR37","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.mad.2017.08.007","volume":"166","author":"K Ngo","year":"2017","unstructured":"Ngo K, et al. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype. Mech Ageing Dev. 2017;166:16\u201323. https:\/\/doi.org\/10.1016\/j.mad.2017.08.007.","journal-title":"Mech Ageing Dev"},{"key":"1962_CR38","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jot.2024.02.003","volume":"45","author":"Y Liu","year":"2024","unstructured":"Liu Y, Dou Y, Sun X, Yang Q. Mechanisms and therapeutic strategies for senescence-associated secretory phenotype in the intervertebral disc degeneration microenvironment. J Orthop Transl. 2024;45:56\u201365. https:\/\/doi.org\/10.1016\/j.jot.2024.02.003.","journal-title":"J Orthop Transl"},{"key":"1962_CR39","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1093\/eurheartj\/ehaa044","volume":"41","author":"HRC Biefer","year":"2020","unstructured":"Biefer HRC, Elkhal A, Cesarovic N, Emmert MY. NAD+ the disregarded molecule in cardiac metabolism. Eur Heart J. 2020;41:983\u20136. https:\/\/doi.org\/10.1093\/eurheartj\/ehaa044.","journal-title":"Eur Heart J"},{"key":"1962_CR40","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41587-019-0377-7","volume":"38","author":"A Patgiri","year":"2020","unstructured":"Patgiri A, et al. An engineered enzyme that targets circulating lactate to alleviate intracellular NADH:NAD(+) imbalance. Nat Biotechnol. 2020;38:309\u201313. https:\/\/doi.org\/10.1038\/s41587-019-0377-7.","journal-title":"Nat Biotechnol"},{"key":"1962_CR41","doi-asserted-by":"publisher","first-page":"47965","DOI":"10.1074\/jbc.X200007200","volume":"277","author":"BL Horecker","year":"2002","unstructured":"Horecker BL. The pentose phosphate pathway. J Biol Chem. 2002;277:47965\u201371. https:\/\/doi.org\/10.1074\/jbc.X200007200.","journal-title":"J Biol Chem"},{"key":"1962_CR42","doi-asserted-by":"publisher","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","volume":"24","author":"M Schieber","year":"2014","unstructured":"Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24:R453-462. https:\/\/doi.org\/10.1016\/j.cub.2014.03.034.","journal-title":"Curr Biol"},{"key":"1962_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.116100","volume":"170","author":"C Yu","year":"2024","unstructured":"Yu C, et al. Hyaluronan delays human amniotic epithelial stem cell senescence by regulating CD44 isoform switch to activate AKT\/mTOR signals. Biomed Pharmacother. 2024;170:116100. https:\/\/doi.org\/10.1016\/j.biopha.2023.116100.","journal-title":"Biomed Pharmacother"},{"key":"1962_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054774","author":"P Galvez-Martin","year":"2023","unstructured":"Galvez-Martin P, et al. A novel hyaluronic acid matrix ingredient with regenerative, anti-aging and antioxidant capacity. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24054774.","journal-title":"Int J Mol Sci"},{"key":"1962_CR45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25010021","author":"MJ Carvalho","year":"2023","unstructured":"Carvalho MJ, et al. Anti-aging potential of a novel ingredient derived from sugarcane straw extract (SSE). Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms25010021.","journal-title":"Int J Mol Sci"},{"key":"1962_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0300-z","volume":"9","author":"G Collin","year":"2018","unstructured":"Collin G, Huna A, Warnier M, Flaman JM, Bernard D. Transcriptional repression of DNA repair genes is a hallmark and a cause of cellular senescence. Cell Death Dis. 2018;9:259. https:\/\/doi.org\/10.1038\/s41419-018-0300-z.","journal-title":"Cell Death Dis"},{"key":"1962_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-07179-1","volume":"7","author":"S Ashraf","year":"2024","unstructured":"Ashraf S, et al. Modulation of ATM enhances DNA repair in G2\/M phase of cell cycle and averts senescence in Fuchs endothelial corneal dystrophy. Commun Biol. 2024;7:1482. https:\/\/doi.org\/10.1038\/s42003-024-07179-1.","journal-title":"Commun Biol"},{"key":"1962_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00821-y","volume":"30","author":"F Chen","year":"2024","unstructured":"Chen F, et al. Bleomycin induces senescence and repression of DNA repair via downregulation of Rad51. Mol Med. 2024;30:54. https:\/\/doi.org\/10.1186\/s10020-024-00821-y.","journal-title":"Mol Med"},{"key":"1962_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1416345","volume":"12","author":"C Li","year":"2024","unstructured":"Li C, et al. Identification and validation of ferroptosis-related biomarkers in intervertebral disc degeneration. Front Cell Dev Biol. 2024;12:1416345. https:\/\/doi.org\/10.3389\/fcell.2024.1416345.","journal-title":"Front Cell Dev Biol"},{"key":"1962_CR50","doi-asserted-by":"publisher","first-page":"125","DOI":"10.23736\/S0390-5616.20.04773-6","volume":"66","author":"H Zhang","year":"2022","unstructured":"Zhang H, et al. Investigation of key miRNAs and their target genes involved in cell apoptosis during intervertebral disc degeneration development using bioinformatics methods. J Neurosurg Sci. 2022;66:125\u201332. https:\/\/doi.org\/10.23736\/S0390-5616.20.04773-6.","journal-title":"J Neurosurg Sci"},{"key":"1962_CR51","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.ajpath.2022.12.014","volume":"193","author":"YG Wang","year":"2023","unstructured":"Wang YG, et al. Ferrostatin-1 inhibits Toll-like receptor 4\/NF-kappaB signaling to alleviate intervertebral disc degeneration in rats. Am J Pathol. 2023;193:430\u201341. https:\/\/doi.org\/10.1016\/j.ajpath.2022.12.014.","journal-title":"Am J Pathol"},{"key":"1962_CR52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1401957","volume":"15","author":"H Zhang","year":"2024","unstructured":"Zhang H, et al. Identification of core genes in intervertebral disc degeneration using bioinformatics and machine learning algorithms. Front Immunol. 2024;15:1401957. https:\/\/doi.org\/10.3389\/fimmu.2024.1401957.","journal-title":"Front Immunol"},{"key":"1962_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103091","volume":"71","author":"S Tamagawa","year":"2024","unstructured":"Tamagawa S, et al. SOD2 orchestrates redox homeostasis in intervertebral discs: a novel insight into oxidative stress-mediated degeneration and therapeutic potential. Redox Biol. 2024;71:103091. https:\/\/doi.org\/10.1016\/j.redox.2024.103091.","journal-title":"Redox Biol"},{"key":"1962_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118929","volume":"267","author":"L Xiao","year":"2021","unstructured":"Xiao L, et al. Sod2 and catalase improve pathological conditions of intervertebral disc degeneration by modifying human adipose-derived mesenchymal stem cells. Life Sci. 2021;267:118929. https:\/\/doi.org\/10.1016\/j.lfs.2020.118929.","journal-title":"Life Sci"},{"key":"1962_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2024.106570","volume":"171","author":"Z Zhang","year":"2024","unstructured":"Zhang Z, et al. INHBA regulates hippo signaling to confer 5-FU chemoresistance mediated by cellular senescence in colon cancer cells. Int J Biochem Cell Biol. 2024;171:106570. https:\/\/doi.org\/10.1016\/j.biocel.2024.106570.","journal-title":"Int J Biochem Cell Biol"},{"key":"1962_CR56","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/cdd.2015.107","volume":"23","author":"SH Jung","year":"2016","unstructured":"Jung SH, et al. Heparan sulfation is essential for the prevention of cellular senescence. Cell Death Differ. 2016;23:417\u201329. https:\/\/doi.org\/10.1038\/cdd.2015.107.","journal-title":"Cell Death Differ"},{"key":"1962_CR57","doi-asserted-by":"publisher","first-page":"10316","DOI":"10.1096\/fj.201902714R","volume":"34","author":"D Kang","year":"2020","unstructured":"Kang D, et al. Sulfated syndecan 1 is critical to preventing cellular senescence by modulating fibroblast growth factor receptor endocytosis. FASEB J. 2020;34:10316\u201328. https:\/\/doi.org\/10.1096\/fj.201902714R.","journal-title":"FASEB J"},{"key":"1962_CR58","doi-asserted-by":"publisher","first-page":"3598","DOI":"10.1182\/bloodadvances.2024014062","volume":"9","author":"I Tosa","year":"2025","unstructured":"Tosa I, et al. BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells. Blood Adv. 2025;9:3598\u2013612. https:\/\/doi.org\/10.1182\/bloodadvances.2024014062.","journal-title":"Blood Adv"},{"key":"1962_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41346-y","volume":"14","author":"L Zhang","year":"2023","unstructured":"Zhang L, et al. CD44 connects autophagy decline and ageing in the vascular endothelium. Nat Commun. 2023;14:5524. https:\/\/doi.org\/10.1038\/s41467-023-41346-y.","journal-title":"Nat Commun"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01962-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-025-01962-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-025-01962-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:04:21Z","timestamp":1789398261000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-025-01962-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["1962"],"URL":"https:\/\/doi.org\/10.1007\/s11357-025-01962-6","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"23 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}