{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:02:22Z","timestamp":1790085742203,"version":"4.0.1"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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:p>Aging-related bone diseases are often interpreted through hormonal decline, defective remodeling, and chronic low-grade inflammation, yet these accounts do not fully capture the cellular, spatial, and temporal heterogeneity of skeletal aging. Bone is an immune-active organ sustained by coordinated signaling among skeletal, hematopoietic, immune, adipose, vascular, and neural compartments. Cellular senescence perturbs this network through stable cell-cycle arrest, metabolic remodeling, and a heterogeneous senescence-associated secretory phenotype (SASP). Whereas recent osteoimmunology syntheses broadly catalog age-related immune\u2013bone interactions, our specific advance is to treat p16- and p21-associated states as functionally non-equivalent and to translate cell identity, anatomical compartment, persistence, and disease stage into explicit therapeutic decision points. We compare senescence programs in bone marrow stromal cells, osteoblast-lineage cells, osteocytes, osteoclast precursors, and immune populations, and then place them within an aging marrow ecosystem shaped by hematopoietic drift, marrow adiposity, vascular decline, and neural degeneration. These mechanisms are mapped across osteoporosis, osteoarthritis, rheumatoid arthritis, periodontitis, and delayed fracture healing. Emerging interventions include senolytics, senomorphics, immune-mediated clearance, bone-targeted delivery, and biomarker-guided patient selection. By operationalizing cell- and stage-resolved therapeutic windows, this framework aims to move senescence-targeted treatment beyond broad senolysis and toward testable precision strategies for aging bone.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1940235","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:19:38Z","timestamp":1790083178000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Osteoimmune senescence in aging bone: from inflammaging dogma to cell-type-specific therapeutic windows"],"prefix":"10.3389","volume":"17","author":[{"given":"Lan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Women\u2019s Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Internal Medicine, Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1186\/s13018-021-02772-0","article-title":"The global prevalence of osteoporosis in the world: a comprehensive systematic review and meta-analysis","volume":"16","author":"Salari","year":"2021","journal-title":"J Orthop Surg Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.21106","article-title":"Prevalence of osteoporosis and fracture in China: The China Osteoporosis Prevalence Study","volume":"4","author":"Wang","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B4","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s11657-021-01009-1","article-title":"Sociodemographic and health system factors associated with variations in hospitalization costs for fractures in adults aged 45 years and over: a cross-sectional study of provincial health accounts in Jiangsu Province, China","volume":"16","author":"Xu","year":"2021","journal-title":"Arch Osteoporos"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10488","article-title":"Bone aging, cellular senescence, and osteoporosis","volume":"5","author":"Pignolo","year":"2021","journal-title":"JBMR Plus"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00727-x","article-title":"The senescence-associated secretory phenotype and its physiological and pathological implications","volume":"25","author":"Wang","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.1115","article-title":"Consequences of aging on bone","volume":"15","author":"Zhang","year":"2024","journal-title":"Aging Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s00223-023-01100-4","article-title":"Bone-SASP in skeletal aging","volume":"113","author":"Fang","year":"2023","journal-title":"Calcif Tissue Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.853765","article-title":"The implications of bone marrow adipose tissue on inflammaging","volume":"13","author":"Aaron","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4385","article-title":"Targeting cellular senescence prevents age-related bone loss in mice","volume":"23","author":"Farr","year":"2017","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.138815","article-title":"Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence","volume":"5","author":"Kim","year":"2020","journal-title":"JCI Insight"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1016\/j.cmet.2021.08.009","article-title":"Senescent immune cells release grancalcin to promote skeletal aging","volume":"33","author":"Li","year":"2021","journal-title":"Cell Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41413-023-00309-1","article-title":"Age-related secretion of grancalcin by macrophages induces skeletal stem\/progenitor cell senescence during fracture healing","volume":"12","author":"Zou","year":"2024","journal-title":"Bone Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102822","article-title":"Osteoimmunology and aging: mechanisms, implications, and therapeutic perspectives","volume":"111","author":"Wang","year":"2025","journal-title":"Ageing Res Rev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13602","article-title":"Targeted clearance of p21- but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity","volume":"21","author":"Chandra","year":"2022","journal-title":"Aging Cell"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI179834","article-title":"Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair","volume":"134","author":"Saul","year":"2024","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03096-2","article-title":"Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial","volume":"30","author":"Farr","year":"2024","journal-title":"Nat Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1267550","article-title":"Age-related changes in human bone marrow mesenchymal stromal cells: morphology, gene expression profile, immunomodulatory activity and miRNA expression","volume":"14","author":"Massaro","year":"2023","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12979-021-00230-3","article-title":"High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges","volume":"18","author":"Nikolaou","year":"2021","journal-title":"Immun Ageing"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2412317122","article-title":"Periarteriolar niches become inflamed in aging bone marrow, remodeling the stromal microenvironment and depleting lymphoid progenitors","volume":"122","author":"Du","year":"2025","journal-title":"Proc Natl Acad Sci USA"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192283","article-title":"Limited rejuvenation of aged hematopoietic stem cells in young bone marrow niche","volume":"218","author":"Kuribayashi","year":"2021","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41467-023-35801-z","article-title":"TGF\u03b21+CCR5+ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice","volume":"14","author":"Li","year":"2023","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00337-5","article-title":"PCLAF induces bone marrow adipocyte senescence and contributes to skeletal aging","volume":"12","author":"Xie","year":"2024","journal-title":"Bone Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7150\/thno.123532","article-title":"The talin1-p53 axis inhibits osteocyte senescence to promote bone mass and mediate skeletal adaptation to mechanical stimulation","volume":"16","author":"Huang","year":"2026","journal-title":"Theranostics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111565","article-title":"The role of senolytics in osteoporosis and other skeletal pathologies","volume":"199","author":"Doolittle","year":"2021","journal-title":"Mech Ageing Dev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.01.015","article-title":"Cellular senescence in bone","volume":"121","author":"Farr","year":"2019","journal-title":"Bone"},{"key":"B27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cyto.2019.01.013","article-title":"The senescence-associated secretory phenotype and its regulation","volume":"117","author":"Lopes-Paciencia","year":"2019","journal-title":"Cytokine"},{"key":"B28","doi-asserted-by":"publisher","first-page":"4827","DOI":"10.1038\/s41467-022-32552-1","article-title":"A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues","volume":"13","author":"Saul","year":"2022","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00738-8","article-title":"SenNet recommendations for detecting senescent cells in different tissues","volume":"25","author":"Suryadevara","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.mocell.2024.100113","article-title":"The role of p21 in cellular senescence and aging-related diseases","volume":"47","author":"Yan","year":"2024","journal-title":"Mol Cells"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204743","article-title":"Key elements of cellular senescence involve transcriptional repression of mitotic and DNA repair genes through the p53-p16\/RB-E2F-DREAM complex","volume":"15","author":"Kandhaya-Pillai","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12344","article-title":"The Achilles' heel of senescent cells: from transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12445","article-title":"Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors","volume":"15","author":"Zhu","year":"2016","journal-title":"Aging Cell"},{"key":"B34","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin is a senotherapeutic that extends health and lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"EBioMedicine"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148073","article-title":"Age-associated callus senescent cells produce TGF-\u03b21 that inhibits fracture healing in aged mice","volume":"132","author":"Liu","year":"2022","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.11.056","article-title":"Bone-targeted delivery of senolytics to eliminate senescent cells increases bone formation in senile osteoporosis","volume":"157","author":"Xing","year":"2023","journal-title":"Acta Biomater"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12075","article-title":"Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK\/NF-kappaB activation","volume":"12","author":"Moiseeva","year":"2013","journal-title":"Aging Cell"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12587","article-title":"Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism","volume":"16","author":"Wang","year":"2017","journal-title":"Aging Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515386112","article-title":"JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age","volume":"112","author":"Xu","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c220012","article-title":"Aging and bone metabolism","volume":"13","author":"Pignolo","year":"2023","journal-title":"Compr Physiol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1111\/acel.12597","article-title":"DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age","volume":"16","author":"Kim","year":"2017","journal-title":"Aging Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.stem.2017.02.009","article-title":"Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration","volume":"20","author":"Ambrosi","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.stem.2021.01.010","article-title":"Loss of KDM4B exacerbates bone-fat imbalance and mesenchymal stromal cell exhaustion in skeletal aging","volume":"28","author":"Deng","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/j.1474-9726.2007.00350.x","article-title":"Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis","volume":"7","author":"Pignolo","year":"2008","journal-title":"Aging Cell"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110632","article-title":"SIRT1 regulates osteoblast senescence through SOD2 acetylation and mitochondrial dysfunction in the progression of osteoporosis caused by cadmium exposure","volume":"382","author":"Zhou","year":"2023","journal-title":"Chem Biol Interact"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-020-00619-x","article-title":"Osteocyte cellular senescence","volume":"18","author":"Farr","year":"2020","journal-title":"Curr Osteoporos Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2892","article-title":"Identification of senescent cells in the bone microenvironment","volume":"31","author":"Farr","year":"2016","journal-title":"J Bone Miner Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93771","article-title":"Old age causes de novo intracortical bone remodeling and porosity in mice","volume":"2","author":"Piemontese","year":"2017","journal-title":"JCI Insight"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81480","article-title":"Osteocytes regulate senescence of bone and bone marrow","volume":"11","author":"Ding","year":"2022","journal-title":"Elife"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69958","article-title":"Modulation of fracture healing by the transient accumulation of senescent cells","volume":"10","author":"Saul","year":"2021","journal-title":"Elife"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00820-8","article-title":"Influences of aged bone marrow macrophages on skeletal health and senescence","volume":"21","author":"Pappert","year":"2023","journal-title":"Curr Osteoporos Rep"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00694-0","article-title":"Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence","volume":"4","author":"Hou","year":"2024","journal-title":"Nat Aging"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12121314","article-title":"Immunosenescence: aging and immune system decline","volume":"12","author":"Goyani","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/35046102","article-title":"T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma","volume":"408","author":"Takayanagi","year":"2000","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11066","article-title":"Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha","volume":"106","author":"Cenci","year":"2000","journal-title":"J Clin Invest"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251534698","article-title":"Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo","volume":"98","author":"Roggia","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B57","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1097\/BOR.0000000000000011","article-title":"T-cell aging in rheumatoid arthritis","volume":"26","author":"Weyand","year":"2014","journal-title":"Curr Opin Rheumatol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00095","article-title":"Senescent T-cells promote bone loss in rheumatoid arthritis","volume":"9","author":"Fessler","year":"2018","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061775","article-title":"Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction","volume":"203","author":"Sato","year":"2006","journal-title":"J Exp Med"},{"key":"B60","doi-asserted-by":"publisher","first-page":"8","DOI":"10.2174\/1876525401406010008","article-title":"B cell production of both OPG and RANKL is significantly increased in aged mice","volume":"6","author":"Li","year":"2014","journal-title":"Open Bone J"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.06.005","article-title":"Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength","volume":"5","author":"Kostenuik","year":"2005","journal-title":"Curr Opin Pharmacol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004497","article-title":"Dysregulated B cell expression of RANKL and OPG correlates with loss of bone mineral density in HIV infection","volume":"10","author":"Titanji","year":"2014","journal-title":"PloS Pathog"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000546107","article-title":"Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis","volume":"107","author":"S\u00f6derstr\u00f6m","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100897","article-title":"NKG2D ligands mediate immunosurveillance of senescent cells","volume":"8","author":"Sagiv","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.705410","article-title":"The hematopoietic bone marrow niche ecosystem","volume":"9","author":"Fr\u00f6bel","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/cells10081849","article-title":"Inflammation and aging of hematopoietic stem cells in their niche","volume":"10","author":"Yang","year":"2021","journal-title":"Cells"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nature12984","article-title":"The bone marrow niche for haematopoietic stem cells","volume":"505","author":"Morrison","year":"2014","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.738204","article-title":"Aging of the hematopoietic stem cell niche: new tools to answer an old question","volume":"12","author":"Matteini","year":"2021","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/nature08099","article-title":"Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment","volume":"460","author":"Naveiras","year":"2009","journal-title":"Nature"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.02.001","article-title":"Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells","volume":"6","author":"Butler","year":"2010","journal-title":"Cell Stem Cell"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nature13145","article-title":"Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone","volume":"507","author":"Kusumbe","year":"2014","journal-title":"Nature"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.36","article-title":"Human type H vessels are a sensitive biomarker of bone mass","volume":"8","author":"Wang","year":"2017","journal-title":"Cell Death Dis"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0030-x","article-title":"Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche","volume":"24","author":"Maryanovich","year":"2018","journal-title":"Nat Med"},{"key":"B74","doi-asserted-by":"publisher","first-page":"3120","DOI":"10.1016\/j.cell.2024.04.013","article-title":"Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging","volume":"187","author":"Bandyopadhyay","year":"2024","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/biology11101419","article-title":"Cellular senescence and periodontitis: mechanisms and therapeutics","volume":"11","author":"Chen","year":"2022","journal-title":"Biol (Basel)"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1177\/00220345241255325","article-title":"Molecular signatures of senescence in periodontitis: clinical insights","volume":"103","author":"Rattanaprukskul","year":"2024","journal-title":"J Dent Res"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95147","article-title":"Senescent cells and osteoarthritis: a painful connection","volume":"128","author":"Jeon","year":"2018","journal-title":"J Clin Invest"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.01.008","article-title":"Aging-related inflammation in osteoarthritis","volume":"23","author":"Greene","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"B79","doi-asserted-by":"publisher","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":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/46303","article-title":"Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand","volume":"402","author":"Kong","year":"1999","journal-title":"Nature"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-019-0169-4","article-title":"Senescent synovial fibroblasts accumulate prematurely in rheumatoid arthritis tissues and display an enhanced inflammatory phenotype","volume":"16","author":"Del Rey","year":"2019","journal-title":"Immun Ageing"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1007\/s40496-018-0202-2","article-title":"Age and periodontal health - immunological view","volume":"5","author":"Ebersole","year":"2018","journal-title":"Curr Oral Health Rep"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.20-0529","article-title":"Senescent cells exacerbate chronic inflammation and contribute to periodontal disease progression in old mice","volume":"92","author":"Aquino-Martinez","year":"2021","journal-title":"J Periodontol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14489","article-title":"Characterization of human senescent cell biomarkers for clinical trials","volume":"24","author":"Farr","year":"2025","journal-title":"Aging Cell"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add1951","article-title":"NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates","volume":"15","author":"Yang","year":"2023","journal-title":"Sci Transl Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6062707","article-title":"Effect of traditional Chinese medicine product, QiangGuYin, on bone mineral density and bone turnover in Chinese postmenopausal osteoporosis","volume":"2017","author":"Shi","year":"2017","journal-title":"Evid Based Complement Alternat Med"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1276631","article-title":"Osteoporosis guidelines on TCM drug therapies: a systematic quality evaluation and content analysis","volume":"14","author":"Zhang","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2365814","article-title":"Ginsenoside Rg1 improves differentiation by inhibiting senescence of human bone marrow mesenchymal stem cell via GSK-3\u03b2 and \u03b2-catenin","volume":"2020","author":"Wang","year":"2020","journal-title":"Stem Cells Int"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.08.007","article-title":"Ginsenoside Rg1 prevents bone marrow mesenchymal stem cell senescence via NRF2 and PI3K\/Akt signaling","volume":"174","author":"Wang","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0200367","article-title":"Flavonoid compound icariin enhances BMP-2 induced differentiation and signalling by targeting to connective tissue growth factor in SAMP6 osteoblasts","volume":"13","author":"Xu","year":"2018","journal-title":"PloS One"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1940235\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:19:39Z","timestamp":1790083179000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1940235\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":90,"alternative-id":["10.3389\/fimmu.2026.1940235"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1940235","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"article-number":"1940235"}}