{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:38:54Z","timestamp":1788921534495,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify cell senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration (IVDD) using bioinformatics and investigate their biological functions and signaling pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GSE56081 and GSE23130 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The former was used for the analysis of differentially expressed genes (DEGs) and the latter was used as the validation set. Intersection analysis of DEGs and cell senescence-related genes was performed to screen for senescence-related differentially expressed genes (SRDEGs). SRDEGs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein\u2013protein interaction (PPI) network was also drawn, and the hub SRDEGs were obtained using 11 different algorithms. Immune infiltration analysis was then performed. Receiver operating characteristic (ROC) curve and quantitative polymerase chain reaction (qPCR) were used to evaluate the diagnostic value of the hub SRDEGs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four hub SRDEGs, SP1, FOXO1, ESR1, and MAPK1, were identified. SP1 was downregulated in IVDD, while the other three hub genes were upregulated. ROC curve verification showed that the AUC for SP1, FOXO1, ESR1, and MAPK1 were 0.483, 0.683, 0.683, and 0.725, respectively. RT-qPCR confirmed that MAPK1 expression was higher in the degeneration group (t = 3.229, P &amp;lt;0.001). Immune infiltration analysis demonstrated elevated proportions of CD8 T cells and activated NK cells in IVDD samples, with MAPK1 showing positive correlations with CD8 T cells, activated NK cells, and neutrophils but negative correlations with naive CD4 T cells, B memory cells, and resting NK cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings highlight MAPK1 as a pivotal regulator of cellular senescence and immune cell infiltration in IVDD pathogenesis, offering novel therapeutic targets for intervention.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1589849","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T04:13:12Z","timestamp":1748491992000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification and validation of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration"],"prefix":"10.3389","volume":"16","author":[{"given":"Hao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30970-9","article-title":"Non-specific low back pain","volume":"389","author":"Maher","year":"2017","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200002150-00016","article-title":"Low back pain in relation to lumbar disc degeneration","volume":"25","author":"Luoma","year":"2000","journal-title":"Spine"},{"key":"B3","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":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1324561","article-title":"Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway","volume":"11","author":"Zhang","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2018.3522","article-title":"Cyclic mechanical tension reinforces DNA damage and activates the p53-p21-Rb pathway to induce premature senescence of nucleus pulposus cells","volume":"41","author":"Feng","year":"2018","journal-title":"Int J Mol medicine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"686","DOI":"10.3390\/biom13040686","article-title":"Cellular senescence in intervertebral disc aging and degeneration: molecular mechanisms and potential therapeutic opportunities","volume":"13","author":"Silwal","year":"2023","journal-title":"Biomolecules"},{"key":"B7","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":"Osteoarthritis cartilage"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.015","article-title":"Senescence in health and disease","volume":"169","author":"He","year":"2017","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","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 medicine"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000253960.57051.de","article-title":"Senescence in cells of the aging and degenerating intervertebral disc: immunolocalization of senescence-associated beta-galactosidase in human and sand rat discs","volume":"32","author":"Gruber","year":"2007","journal-title":"Spine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1196","article-title":"The involvement of immune system in intervertebral disc herniation and degeneration","volume":"5","author":"Ye","year":"2022","journal-title":"JOR spine"},{"key":"B12","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1186\/s13075-014-0465-5","article-title":"Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study","volume":"16","author":"Wan","year":"2014","journal-title":"Arthritis Res Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1744-8069-8-63","article-title":"Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus","volume":"8","author":"Gruber","year":"2012","journal-title":"Mol pain"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad927","article-title":"Human Ageing Genomic Resources: updates on key databases in ageing research","volume":"52","author":"de Magalh\u00e3es","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.608349","article-title":"Identification and characterization of biomarkers and their role in opioid addiction by integrated bioinformatics analysis","volume":"14","author":"Zhang","year":"2020","journal-title":"Front Neurosci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.12.003","article-title":"Several concerns on grading lumbar disc degeneration on MR image with Pfirrmann criteria","volume":"32","author":"Wang","year":"2022","journal-title":"J orthopaedic translation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.3390\/ijms23031715","article-title":"The proteolysis of ECM in intervertebral disc degeneration","volume":"23","author":"Liang","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"101767","DOI":"10.1016\/j.arr.2022.101767","article-title":"Potential mechanisms underlying the accelerated cognitive decline in people with chronic low back pain: A scoping review","volume":"82","author":"Zhou","year":"2022","journal-title":"Ageing Res Rev"},{"key":"B19","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 Cells materials"},{"key":"B20","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s13075-017-1384-z","article-title":"High-magnitude compression accelerates the premature senescence of nucleus pulposus cells via the p38 MAPK-ROS pathway","volume":"19","author":"Li","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"B21","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/bs.ircmb.2014.09.002","article-title":"The amazing ubiquitin-proteasome system: structural components and implication in aging","volume":"314","author":"Tsakiri","year":"2015","journal-title":"Int Rev Cell Mol Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.neuron.2024.09.015","article-title":"Autophagy, aging, and age-related neurodegeneration","volume":"113","author":"Palmer","year":"2025","journal-title":"Neuron"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.11.003","article-title":"Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis","volume":"14","author":"Nogueira","year":"2008","journal-title":"Cancer Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206701","article-title":"MAPK pathways in radiation responses","volume":"22","author":"Dent","year":"2003","journal-title":"Oncogene"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3109\/10799893.2015.1030412","article-title":"Signaling pathway of MAPK\/ERK in cell proliferation, differentiation, migration, senescence and apoptosis","volume":"35","author":"Sun","year":"2015","journal-title":"J receptor Signal transduction Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808116200","article-title":"Oxidative stress is linked to ERK1\/2-p16 signaling-mediated growth defect in ATM-deficient astrocytes","volume":"284","author":"Kim","year":"2009","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202300130","article-title":"Prenatal DEHP exposure induces premature testicular aging by promoting leydig cell senescence through the MAPK signaling pathways","volume":"7","author":"Qigen","year":"2023","journal-title":"Advanced Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"102429","DOI":"10.1016\/j.arr.2024.102429","article-title":"Pivotal role of AGE-RAGE axis in brain aging with current interventions","volume":"100","author":"Vitorakis","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13325","article-title":"Proteomics in aging research: A roadmap to clinical, translational research","volume":"20","author":"Moaddel","year":"2021","journal-title":"Aging Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.666355","article-title":"Revealing the immune infiltration landscape and identifying diagnostic biomarkers for lumbar disc herniation","volume":"12","author":"Wang","year":"2021","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203999","article-title":"Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts","volume":"14","author":"Nojima","year":"2022","journal-title":"Aging"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.08.014","article-title":"Depletion of ERK2 but not ERK1 abrogates oncogenic Ras-induced senescence","volume":"25","author":"Shin","year":"2013","journal-title":"Cell signalling"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.11817\/j.issn.1672-7347","article-title":"Research advances in the role of MAPK cascade in regulation of cell growth, immunity, inflammation, and cancer","volume":"47","author":"Gong","year":"2022","journal-title":"Zhong nan da xue xue bao Yi xue ban"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9712","article-title":"Mechanisms shaping the role of ERK1\/2 in cellular senescence (Review)","volume":"19","author":"Zou","year":"2019","journal-title":"Mol Med reports"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.02.001","article-title":"Hallmarks of cellular senescence","volume":"28","author":"Hernandez-Segura","year":"2018","journal-title":"Trends Cell Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/gad.203984.112","article-title":"Tumor suppressor activity of the ERK\/MAPK pathway by promoting selective protein degradation","volume":"27","author":"Desch\u00eanes-Simard","year":"2013","journal-title":"Genes Dev"},{"key":"B37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1146\/annurev.immunol.20.091301.131133","article-title":"MAP kinases in the immune response","volume":"20","author":"Dong","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1186\/s12974-016-0690-8","article-title":"The crucial role of Erk2 in demyelinating inflammation in the central nervous system","volume":"13","author":"Okazaki","year":"2016","journal-title":"J neuroinflammation"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1589849\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T04:13:14Z","timestamp":1748491994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1589849\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2025.1589849"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1589849","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"article-number":"1589849"}}