{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T05:04:38Z","timestamp":1794546278993,"version":"4.9.1"},"reference-count":97,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Aging"],"DOI":"10.1038\/s43587-025-00910-5","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T15:03:02Z","timestamp":1755183782000},"page":"1415-1424","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Immune surveillance of senescent cells in aging and disease"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-2113","authenticated-orcid":false,"given":"Julia","family":"Majewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3977-5482","authenticated-orcid":false,"given":"Valery","family":"Krizhanovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"910_CR1","doi-asserted-by":"publisher","first-page":"4150","DOI":"10.1016\/j.cell.2024.05.059","volume":"187","author":"M Ogrodnik","year":"2024","unstructured":"Ogrodnik, M. et al. Guidelines for minimal information on cellular senescence experimentation in vivo. Cell 187, 4150\u20134175 (2024).","journal-title":"Cell"},{"key":"910_CR2","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","volume":"22","author":"R Di Micco","year":"2021","unstructured":"Di Micco, R., Krizhanovsky, V., Baker, D., & d\u2019Adda di Fagagna, F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat. Rev. Mol. Cell Biol. 22, 75\u201395 (2021).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"910_CR3","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1101\/gad.227512.113","volume":"27","author":"A Chuprin","year":"2013","unstructured":"Chuprin, A. et al. Cell fusion induced by ERVWE1 or measles virus causes cellular senescence. Genes Dev. 27, 2356\u20132366 (2013).","journal-title":"Genes Dev."},{"key":"910_CR4","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.devcel.2014.11.012","volume":"31","author":"M Demaria","year":"2014","unstructured":"Demaria, M. et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722\u2013733 (2014).","journal-title":"Dev. Cell"},{"key":"910_CR5","doi-asserted-by":"publisher","first-page":"e100849","DOI":"10.15252\/embj.2018100849","volume":"38","author":"H Gal","year":"2019","unstructured":"Gal, H. et al. Molecular pathways of senescence regulate placental structure and function. EMBO J. 38, e100849 (2019).","journal-title":"EMBO J."},{"key":"910_CR6","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1101\/sqb.2008.73.048","volume":"73","author":"V Krizhanovsky","year":"2008","unstructured":"Krizhanovsky, V. et al. Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb. Symp. Quant. Biol. 73, 513\u2013522 (2008).","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"910_CR7","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cell.2008.06.049","volume":"134","author":"V Krizhanovsky","year":"2008","unstructured":"Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657\u2013667 (2008).","journal-title":"Cell"},{"key":"910_CR8","doi-asserted-by":"publisher","first-page":"aaf4445","DOI":"10.1126\/science.aaf4445","volume":"354","author":"L Mosteiro","year":"2016","unstructured":"Mosteiro, L. et al. Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science 354, aaf4445 (2016).","journal-title":"Science"},{"key":"910_CR9","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.cell.2013.10.019","volume":"155","author":"D Mu\u00f1oz-Esp\u00edn","year":"2013","unstructured":"Mu\u00f1oz-Esp\u00edn, D. et al. Programmed cell senescence during mammalian embryonic development. Cell 155, 1104\u20131118 (2013).","journal-title":"Cell"},{"key":"910_CR10","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.cell.2013.10.041","volume":"155","author":"M Storer","year":"2013","unstructured":"Storer, M. et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 155, 1119\u20131130 (2013).","journal-title":"Cell"},{"key":"910_CR11","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S0092-8674(00)81902-9","volume":"88","author":"M Serrano","year":"1997","unstructured":"Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593\u2013602 (1997).","journal-title":"Cell"},{"key":"910_CR12","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","volume":"5","author":"J-P Copp\u00e9","year":"2010","unstructured":"Copp\u00e9, J.-P., Desprez, P.-Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99\u2013118 (2010).","journal-title":"Annu. Rev. Pathol."},{"key":"910_CR13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nrc2560","volume":"9","author":"T Kuilman","year":"2009","unstructured":"Kuilman, T. & Peeper, D. S. Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer 9, 81\u201394 (2009).","journal-title":"Nat. Rev. Cancer"},{"key":"910_CR14","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1038\/nrm3823","volume":"15","author":"D Mu\u00f1oz-Esp\u00edn","year":"2014","unstructured":"Mu\u00f1oz-Esp\u00edn, D. & Serrano, M. Cellular senescence: from physiology to pathology. Nat. Rev. Mol. Cell Biol. 15, 482\u2013496 (2014).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"910_CR15","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/ncb2784","volume":"15","author":"JC Acosta","year":"2013","unstructured":"Acosta, J. C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15, 978\u2013990 (2013).","journal-title":"Nat. Cell Biol."},{"key":"910_CR16","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1093\/gerona\/glu057","volume":"69","author":"C Franceschi","year":"2014","unstructured":"Franceschi, C. & Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69, S4\u2013S9 (2014).","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"910_CR17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1083\/jcb.201708092","volume":"217","author":"D McHugh","year":"2018","unstructured":"McHugh, D. & Gil, J. Senescence and aging: causes, consequences, and therapeutic avenues. J. Cell Biol. 217, 65\u201377 (2018).","journal-title":"J. Cell Biol."},{"key":"910_CR18","doi-asserted-by":"publisher","first-page":"866718","DOI":"10.3389\/fragi.2022.866718","volume":"3","author":"A Mylonas","year":"2022","unstructured":"Mylonas, A. & O\u2019Loghlen, A. Cellular senescence and ageing: mechanisms and interventions. Front. Aging 3, 866718 (2022).","journal-title":"Front. Aging"},{"key":"910_CR19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/d41586-024-00538-2","volume":"627","author":"J Vijg","year":"2024","unstructured":"Vijg, J. & Hoeijmakers, J. Judith Campisi (1948\u20132024), cell biologist who explored how cells age. Nature 627, 29 (2024).","journal-title":"Nature"},{"key":"910_CR20","doi-asserted-by":"publisher","first-page":"5495","DOI":"10.1038\/s41467-019-13192-4","volume":"10","author":"O Karin","year":"2019","unstructured":"Karin, O., Agrawal, A., Porat, Z., Krizhanovsky, V. & Alon, U. Senescent cell turnover slows with age providing an explanation for the Gompertz law. Nat. Commun. 10, 5495 (2019).","journal-title":"Nat. Commun."},{"key":"910_CR21","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s43587-025-00803-7","volume":"5","author":"J Majewska","year":"2025","unstructured":"Majewska, J. & Krizhanovsky, V. GD3 ganglioside checkpoints in immune surveillance of senescent cells. Nat. Aging 5, 182\u2013183 (2025).","journal-title":"Nat. Aging"},{"key":"910_CR22","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1038\/s41556-024-01465-0","volume":"26","author":"J Majewska","year":"2024","unstructured":"Majewska, J. et al. p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells. Nat. Cell Biol. 26, 1336\u20131345 (2024).","journal-title":"Nat. Cell Biol."},{"key":"910_CR23","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/s41586-022-05388-4","volume":"611","author":"T-W Wang","year":"2022","unstructured":"Wang, T.-W. et al. Blocking PD-L1\u2013PD-1 improves senescence surveillance and ageing phenotypes. Nature 611, 358\u2013364 (2022).","journal-title":"Nature"},{"key":"910_CR24","doi-asserted-by":"publisher","first-page":"3503","DOI":"10.1182\/blood-2008-08-173914","volume":"113","author":"A Soriani","year":"2009","unstructured":"Soriani, A. et al. ATM\u2013ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. Blood 113, 3503\u20133511 (2009).","journal-title":"Blood"},{"key":"910_CR25","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/nature05529","volume":"445","author":"W Xue","year":"2007","unstructured":"Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656\u2013660 (2007).","journal-title":"Nature"},{"key":"910_CR26","doi-asserted-by":"publisher","first-page":"5435","DOI":"10.1038\/s41467-018-07825-3","volume":"9","author":"Y Ovadya","year":"2018","unstructured":"Ovadya, Y. et al. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat. Commun. 9, 5435 (2018).","journal-title":"Nat. Commun."},{"key":"910_CR27","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1038\/onc.2012.206","volume":"32","author":"A Sagiv","year":"2013","unstructured":"Sagiv, A. et al. Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 32, 1971\u20131977 (2013).","journal-title":"Oncogene"},{"key":"910_CR28","doi-asserted-by":"publisher","first-page":"328","DOI":"10.18632\/aging.100897","volume":"8","author":"A Sagiv","year":"2016","unstructured":"Sagiv, A. et al. NKG2D ligands mediate immunosurveillance of senescent cells. Aging 8, 328\u2013344 (2016).","journal-title":"Aging"},{"key":"910_CR29","doi-asserted-by":"publisher","first-page":"e31274","DOI":"10.7554\/eLife.31274","volume":"6","author":"PJ Brighton","year":"2017","unstructured":"Brighton, P. J. et al. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. eLife 6, e31274 (2017).","journal-title":"eLife"},{"key":"910_CR30","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1126\/science.285.5428.727","volume":"285","author":"S Bauer","year":"1999","unstructured":"Bauer, S. et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285, 727\u2013729 (1999).","journal-title":"Science"},{"key":"910_CR31","doi-asserted-by":"publisher","first-page":"e26663","DOI":"10.4161\/onci.26663","volume":"2","author":"A Soriani","year":"2013","unstructured":"Soriani, A. et al. Chemotherapy-elicited upregulation of NKG2D and DNAM-1 ligands as a therapeutic target in multiple myeloma. Oncoimmunology 2, e26663 (2013).","journal-title":"Oncoimmunology"},{"key":"910_CR32","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1210\/en.2016-1886","volume":"158","author":"M Egashira","year":"2017","unstructured":"Egashira, M. et al. F4\/80+ macrophages contribute to clearance of senescent cells in the mouse postpartum uterus. Endocrinology 158, 2344\u20132353 (2017).","journal-title":"Endocrinology"},{"key":"910_CR33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3389\/fimmu.2018.00127","volume":"9","author":"S Gordon","year":"2018","unstructured":"Gordon, S. & Pl\u00fcddemann, A. Macrophage clearance of apoptotic cells: a critical assessment. Front. Immunol. 9, 127 (2018).","journal-title":"Front. Immunol."},{"key":"910_CR34","doi-asserted-by":"publisher","first-page":"342","DOI":"10.4049\/jimmunol.175.1.342","volume":"175","author":"RD Stout","year":"2005","unstructured":"Stout, R. D. et al. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J. Immunol. 175, 342\u2013349 (2005).","journal-title":"J. Immunol."},{"key":"910_CR35","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.cell.2013.03.020","volume":"153","author":"A Lujambio","year":"2013","unstructured":"Lujambio, A. et al. Non-cell-autonomous tumor suppression by p53. Cell 153, 449\u2013460 (2013).","journal-title":"Cell"},{"key":"910_CR36","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41573-022-00520-5","volume":"21","author":"A Mantovani","year":"2022","unstructured":"Mantovani, A., Allavena, P., Marchesi, F. & Garlanda, C. Macrophages as tools and targets in cancer therapy. Nat. Rev. Drug Discov. 21, 799\u2013820 (2022).","journal-title":"Nat. Rev. Drug Discov."},{"key":"910_CR37","doi-asserted-by":"publisher","first-page":"eabb3420","DOI":"10.1126\/science.abb3420","volume":"374","author":"I Sturmlechner","year":"2021","unstructured":"Sturmlechner, I. et al. p21 produces a bioactive secretome that places stressed cells under immunosurveillance. Science 374, eabb3420 (2021).","journal-title":"Science"},{"key":"910_CR38","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.18632\/aging.204622","volume":"15","author":"N Levi","year":"2023","unstructured":"Levi, N. et al. p21 facilitates chronic lung inflammation via epithelial and endothelial cells. Aging 15, 2395\u20132417 (2023).","journal-title":"Aging"},{"key":"910_CR39","doi-asserted-by":"publisher","first-page":"5360","DOI":"10.1038\/s44318-024-00246-7","volume":"43","author":"N Papismadov","year":"2024","unstructured":"Papismadov, N. et al. p21 regulates expression of ECM components and promotes pulmonary fibrosis via CDK4 and Rb. EMBO J. 43, 5360\u20135380 (2024).","journal-title":"EMBO J."},{"key":"910_CR40","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.cell.2019.05.041","volume":"178","author":"C-H Hsu","year":"2019","unstructured":"Hsu, C.-H., Altschuler, S. J. & Wu, L. F. Patterns of early p21 dynamics determine proliferation\u2013senescence cell fate after chemotherapy. Cell 178, 361\u2013373 (2019).","journal-title":"Cell"},{"key":"910_CR41","doi-asserted-by":"publisher","first-page":"8689","DOI":"10.3390\/ijms23158689","volume":"23","author":"R Zheng","year":"2022","unstructured":"Zheng, R. et al. The complement system, aging, and aging-related diseases. Int. J. Mol. Sci. 23, 8689 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"910_CR42","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1158\/2159-8290.CD-22-0523","volume":"13","author":"I Marin","year":"2023","unstructured":"Marin, I. et al. Cellular senescence is immunogenic and promotes antitumor immunity. Cancer Discov. 13, 410\u2013431 (2023).","journal-title":"Cancer Discov."},{"key":"910_CR43","doi-asserted-by":"publisher","first-page":"2652","DOI":"10.1016\/j.cub.2017.07.033","volume":"27","author":"A Hernandez-Segura","year":"2017","unstructured":"Hernandez-Segura, A. et al. Unmasking transcriptional heterogeneity in senescent cells. Curr. Biol. 27, 2652\u20132660 (2017).","journal-title":"Curr. Biol."},{"key":"910_CR44","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1111\/imcb.12727","volume":"102","author":"AH Abu-Humaidan","year":"2024","unstructured":"Abu-Humaidan, A. H. et al. Therapy-induced senescent cancer cells exhibit complement activation and increased complement regulatory protein expression. Immunol. Cell Biol. 102, 240\u2013255 (2024).","journal-title":"Immunol. Cell Biol."},{"key":"910_CR45","doi-asserted-by":"publisher","first-page":"4382","DOI":"10.18632\/aging.102059","volume":"11","author":"G Castellano","year":"2019","unstructured":"Castellano, G. et al. Complement component C5a induces aberrant epigenetic modifications in renal tubular epithelial cells accelerating senescence by Wnt4\/\u03b2catenin signaling after ischemia\/reperfusion injury. Aging 11, 4382\u20134406 (2019).","journal-title":"Aging"},{"key":"910_CR46","doi-asserted-by":"publisher","unstructured":"Debiesse, A. et al. Oncogenic stress is a novel immunogenic signal driven by the unfolded protein response and detected by neutrophils. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.01.17.633444 (2025).","DOI":"10.1101\/2025.01.17.633444"},{"key":"910_CR47","doi-asserted-by":"publisher","first-page":"eaay5356","DOI":"10.1126\/science.aay5356","volume":"369","author":"F Binet","year":"2020","unstructured":"Binet, F. et al. Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy. Science 369, eaay5356 (2020).","journal-title":"Science"},{"key":"910_CR48","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/nature10599","volume":"479","author":"T-W Kang","year":"2011","unstructured":"Kang, T.-W. et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547\u2013551 (2011).","journal-title":"Nature"},{"key":"910_CR49","doi-asserted-by":"publisher","first-page":"e14011","DOI":"10.1111\/acel.14011","volume":"22","author":"Y Lin","year":"2023","unstructured":"Lin, Y. et al. Circulating monocytes expressing senescence-associated features are enriched in COVID-19 patients with severe disease. Aging Cell 22, e14011 (2023).","journal-title":"Aging Cell"},{"key":"910_CR50","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/s41577-022-00785-2","volume":"23","author":"CA Schmitt","year":"2023","unstructured":"Schmitt, C. A. et al. COVID-19 and cellular senescence. Nat. Rev. Immunol. 23, 251\u2013263 (2023).","journal-title":"Nat. Rev. Immunol."},{"key":"910_CR51","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/j.cell.2023.02.033","volume":"186","author":"T Hasegawa","year":"2023","unstructured":"Hasegawa, T. et al. Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus antigen. Cell 186, 1417\u20131431 (2023).","journal-title":"Cell"},{"key":"910_CR52","doi-asserted-by":"publisher","unstructured":"Elyahu, Y. et al. CD4 T cells acquire cytotoxic properties to modulate cellular senescence and aging. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.01.14.575313 (2024).","DOI":"10.1101\/2024.01.14.575313"},{"key":"910_CR53","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1158\/2159-8290.CD-22-0528","volume":"13","author":"H-A Chen","year":"2023","unstructured":"Chen, H.-A. et al. Senescence rewires microenvironment sensing to facilitate antitumor immunity. Cancer Discov. 13, 432\u2013453 (2023).","journal-title":"Cancer Discov."},{"key":"910_CR54","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1182\/blood.2020005244","volume":"137","author":"M Reimann","year":"2021","unstructured":"Reimann, M. et al. Adaptive T-cell immunity controls senescence-prone MyD88- or CARD11-mutant B-cell lymphomas. Blood 137, 2785\u20132799 (2021).","journal-title":"Blood"},{"key":"910_CR55","doi-asserted-by":"publisher","first-page":"E1668","DOI":"10.1073\/pnas.1614661114","volume":"114","author":"D Frescas","year":"2017","unstructured":"Frescas, D. et al. Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody. Proc. Natl Acad. Sci. USA 114, E1668\u2013E1677 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"910_CR56","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1038\/s41467-019-10335-5","volume":"10","author":"BI Pereira","year":"2019","unstructured":"Pereira, B. I. et al. Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nat. Commun. 10, 2387 (2019).","journal-title":"Nat. Commun."},{"key":"910_CR57","doi-asserted-by":"publisher","first-page":"e13434","DOI":"10.1111\/imr.13434","volume":"329","author":"GM Gillespie","year":"2025","unstructured":"Gillespie, G. M., Quastel, M. N. & McMichael, A. J. HLA-E: immune receptor functional mechanisms revealed by structural studies. Immunol. Rev. 329, e13434 (2025).","journal-title":"Immunol. Rev."},{"key":"910_CR58","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/s43587-024-00776-z","volume":"5","author":"C Iltis","year":"2025","unstructured":"Iltis, C. et al. A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging. Nat. Aging 5, 219\u2013236 (2025).","journal-title":"Nat. Aging"},{"key":"910_CR59","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nature18935","volume":"536","author":"Y Kojima","year":"2016","unstructured":"Kojima, Y. et al. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature 536, 86\u201390 (2016).","journal-title":"Nature"},{"key":"910_CR60","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/s41423-020-00541-3","volume":"18","author":"DM Mosser","year":"2021","unstructured":"Mosser, D. M., Hamidzadeh, K. & Goncalves, R. Macrophages and the maintenance of homeostasis. Cell. Mol. Immunol. 18, 579\u2013587 (2021).","journal-title":"Cell. Mol. Immunol."},{"key":"910_CR61","doi-asserted-by":"publisher","first-page":"e202207097","DOI":"10.1083\/jcb.202207097","volume":"222","author":"D Schloesser","year":"2023","unstructured":"Schloesser, D. et al. Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47\u2013QPCT\/L axis. J. Cell Biol. 222, e202207097 (2023).","journal-title":"J. Cell Biol."},{"key":"910_CR62","doi-asserted-by":"publisher","first-page":"736","DOI":"10.4049\/jimmunol.1402643","volume":"195","author":"A Zingoni","year":"2015","unstructured":"Zingoni, A. et al. Genotoxic stress induces senescence-associated ADAM10-dependent release of NKG2D MIC ligands in multiple myeloma cells. J. Immunol. 195, 736\u2013748 (2015).","journal-title":"J. Immunol."},{"key":"910_CR63","doi-asserted-by":"publisher","first-page":"447","DOI":"10.3389\/fimmu.2020.00447","volume":"11","author":"A Zingoni","year":"2020","unstructured":"Zingoni, A., Vulpis, E., Loconte, L. & Santoni, A. NKG2D ligand shedding in response to stress: role of ADAM10. Front. Immunol. 11, 447 (2020).","journal-title":"Front. Immunol."},{"key":"910_CR64","doi-asserted-by":"publisher","first-page":"e0017122","DOI":"10.1128\/mcb.00171-22","volume":"42","author":"A Onorati","year":"2022","unstructured":"Onorati, A. et al. Upregulation of PD-L1 in senescence and aging. Mol. Cell. Biol. 42, e0017122 (2022).","journal-title":"Mol. Cell. Biol."},{"key":"910_CR65","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/s43018-023-00712-x","volume":"5","author":"S Chaib","year":"2024","unstructured":"Chaib, S. et al. The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2. Nat. Cancer 5, 448\u2013462 (2024).","journal-title":"Nat. Cancer"},{"key":"910_CR66","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41586-021-03547-7","volume":"594","author":"MJ Yousefzadeh","year":"2021","unstructured":"Yousefzadeh, M. J. et al. An aged immune system drives senescence and ageing of solid organs. Nature 594, 100\u2013105 (2021).","journal-title":"Nature"},{"key":"910_CR67","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1038\/s43587-024-00694-0","volume":"4","author":"J Hou","year":"2024","unstructured":"Hou, J. et al. Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence. Nat. Aging 4, 1562\u20131581 (2024).","journal-title":"Nat. Aging"},{"key":"910_CR68","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1016\/j.ccell.2023.05.004","volume":"41","author":"S Haston","year":"2023","unstructured":"Haston, S. et al. Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer. Cancer Cell 41, 1242\u20131260 (2023).","journal-title":"Cancer Cell"},{"key":"910_CR69","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.18632\/aging.101268","volume":"9","author":"BM Hall","year":"2017","unstructured":"Hall, B. M. et al. p16(Ink4a) and senescence-associated \u03b2-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging 9, 1867\u20131884 (2017).","journal-title":"Aging"},{"key":"910_CR70","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.18632\/aging.100991","volume":"8","author":"BM Hall","year":"2016","unstructured":"Hall, B. M. et al. Aging of mice is associated with p16(Ink4a)- and \u03b2-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells. Aging 8, 1294\u20131315 (2016).","journal-title":"Aging"},{"key":"910_CR71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2020.12.003","volume":"230","author":"RPH De Maeyer","year":"2021","unstructured":"De Maeyer, R. P. H. & Chambers, E. S. The impact of ageing on monocytes and macrophages. Immunol. Lett. 230, 1\u201310 (2021).","journal-title":"Immunol. Lett."},{"key":"910_CR72","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1038\/s41467-024-47317-1","volume":"15","author":"Y Fan","year":"2024","unstructured":"Fan, Y. et al. Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice. Nat. Commun. 15, 2939 (2024).","journal-title":"Nat. Commun."},{"key":"910_CR73","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/s41593-024-01620-8","volume":"27","author":"N Rachmian","year":"2024","unstructured":"Rachmian, N. et al. Identification of senescent, TREM2-expressing microglia in aging and Alzheimer\u2019s disease model mouse brain. Nat. Neurosci. 27, 1116\u20131124 (2024).","journal-title":"Nat. Neurosci."},{"key":"910_CR74","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/j.ccell.2023.05.006","volume":"41","author":"LI Prieto","year":"2023","unstructured":"Prieto, L. I. et al. Senescent alveolar macrophages promote early-stage lung tumorigenesis. Cancer Cell 41, 1261\u20131275 (2023).","journal-title":"Cancer Cell"},{"key":"910_CR75","doi-asserted-by":"publisher","first-page":"e106048","DOI":"10.15252\/embj.2020106048","volume":"40","author":"A Lagnado","year":"2021","unstructured":"Lagnado, A. et al. Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner. EMBO J. 40, e106048 (2021).","journal-title":"EMBO J."},{"key":"910_CR76","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.immuni.2020.11.005","volume":"54","author":"DA Mogilenko","year":"2021","unstructured":"Mogilenko, D. A. et al. Comprehensive profiling of an aging immune system reveals clonal GZMK+ CD8+ T cells as conserved hallmark of inflammaging. Immunity 54, 99\u2013115 (2021).","journal-title":"Immunity"},{"key":"910_CR77","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1101\/gad.343129.120","volume":"34","author":"J Birch","year":"2020","unstructured":"Birch, J. & Gil, J. Senescence and the SASP: many therapeutic avenues. Genes Dev. 34, 1565\u20131576 (2020).","journal-title":"Genes Dev."},{"key":"910_CR78","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1126\/science.aax0860","volume":"368","author":"G Desd\u00edn-Mic\u00f3","year":"2020","unstructured":"Desd\u00edn-Mic\u00f3, G. et al. T cells with dysfunctional mitochondria induce multimorbidity and premature senescence. Science 368, 1371\u20131376 (2020).","journal-title":"Science"},{"key":"910_CR79","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nature11824","volume":"494","author":"H Braum\u00fcller","year":"2013","unstructured":"Braum\u00fcller, H. et al. T-helper-1-cell cytokines drive cancer into senescence. Nature 494, 361\u2013365 (2013).","journal-title":"Nature"},{"key":"910_CR80","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1111\/cas.15824","volume":"114","author":"T Kakuda","year":"2023","unstructured":"Kakuda, T. et al. Senescent CD8+ T cells acquire NK cell-like innate functions to promote antitumor immunity. Cancer Sci. 114, 2810\u20132820 (2023).","journal-title":"Cancer Sci."},{"key":"910_CR81","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/s41590-022-01141-1","volume":"23","author":"AC Huang","year":"2022","unstructured":"Huang, A. C. & Zappasodi, R. A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance. Nat. Immunol. 23, 660\u2013670 (2022).","journal-title":"Nat. Immunol."},{"key":"910_CR82","doi-asserted-by":"publisher","unstructured":"Fissoun, C. et al. The ganglioside GD3 and its synthase (ST8SIA1) as novel senescence markers associated with osteoarthritis. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.03.22.640206 (2025).","DOI":"10.1101\/2025.03.22.640206"},{"key":"910_CR83","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/s43587-024-00642-y","volume":"4","author":"G Katsuumi","year":"2024","unstructured":"Katsuumi, G. et al. SGLT2 inhibition eliminates senescent cells and alleviates pathological aging. Nat. Aging 4, 926\u2013938 (2024).","journal-title":"Nat. Aging"},{"key":"910_CR84","doi-asserted-by":"publisher","first-page":"20358","DOI":"10.1038\/s41598-021-99852-2","volume":"11","author":"M Poblocka","year":"2021","unstructured":"Poblocka, M. et al. Targeted clearance of senescent cells using an antibody\u2013drug conjugate against a specific membrane marker. Sci. Rep. 11, 20358 (2021).","journal-title":"Sci. Rep."},{"key":"910_CR85","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/s41586-020-2403-9","volume":"583","author":"C Amor","year":"2020","unstructured":"Amor, C. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583, 127\u2013132 (2020).","journal-title":"Nature"},{"key":"910_CR86","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/s43587-023-00560-5","volume":"4","author":"C Amor","year":"2024","unstructured":"Amor, C. et al. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat. Aging 4, 336\u2013349 (2024).","journal-title":"Nat. Aging"},{"key":"910_CR87","doi-asserted-by":"publisher","first-page":"eadd1951","DOI":"10.1126\/scitranslmed.add1951","volume":"15","author":"D Yang","year":"2023","unstructured":"Yang, D. et al. NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates. Sci. Transl. Med. 15, eadd1951 (2023).","journal-title":"Sci. Transl. Med."},{"key":"910_CR88","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s43587-024-00750-9","volume":"5","author":"X Ming","year":"2025","unstructured":"Ming, X. et al. A chimeric peptide promotes immune surveillance of senescent cells in injury, fibrosis, tumorigenesis and aging. Nat. Aging 5, 28\u201347 (2025).","journal-title":"Nat. Aging"},{"key":"910_CR89","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","volume":"21","author":"AJ Pollard","year":"2021","unstructured":"Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83\u2013100 (2021).","journal-title":"Nat. Rev. Immunol."},{"key":"910_CR90","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/0006-8993(88)90671-3","volume":"474","author":"H Yagi","year":"1988","unstructured":"Yagi, H., Katoh, S., Akiguchi, I. & Takeda, T. Age-related deterioration of ability of acquisition in memory and learning in senescence accelerated mouse: SAM-P\/8 as an animal model of disturbances in recent memory. Brain Res. 474, 86\u201393 (1988).","journal-title":"Brain Res."},{"key":"910_CR91","doi-asserted-by":"publisher","first-page":"102431","DOI":"10.1016\/j.coi.2024.102431","volume":"88","author":"P Paparoditis","year":"2024","unstructured":"Paparoditis, P. & Shulman, Z. The tumor-driven antibody-mediated immune response in cancer. Curr. Opin. Immunol. 88, 102431 (2024).","journal-title":"Curr. Opin. Immunol."},{"key":"910_CR92","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/s43587-021-00151-2","volume":"1","author":"M Suda","year":"2021","unstructured":"Suda, M. et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat. Aging 1, 1117\u20131126 (2021).","journal-title":"Nat. Aging"},{"key":"910_CR93","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1101\/gad.302570.117","volume":"31","author":"KM Kim","year":"2017","unstructured":"Kim, K. M. et al. Identification of senescent cell surface targetable protein DPP4. Genes Dev. 31, 1529\u20131534 (2017).","journal-title":"Genes Dev."},{"key":"910_CR94","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1038\/s41467-020-16347-w","volume":"11","author":"S Yoshida","year":"2020","unstructured":"Yoshida, S. et al. The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice. Nat. Commun. 11, 2482 (2020).","journal-title":"Nat. Commun."},{"key":"910_CR95","doi-asserted-by":"publisher","unstructured":"Triana-Martinez, F. et al. p16High immune cell-controlled disease tolerance as a broad defense and healthspan extending strategy. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.07.15.603540 (2024).","DOI":"10.1101\/2024.07.15.603540"},{"key":"910_CR96","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/s43587-023-00442-w","volume":"3","author":"L Delval","year":"2023","unstructured":"Delval, L. et al. Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters. Nat. Aging 3, 829\u2013845 (2023).","journal-title":"Nat. Aging"},{"key":"910_CR97","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41586-021-03995-1","volume":"599","author":"S Lee","year":"2021","unstructured":"Lee, S. et al. Virus-induced senescence is a driver and therapeutic target in COVID-19. Nature 599, 283\u2013289 (2021).","journal-title":"Nature"}],"container-title":["Nature Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s43587-025-00910-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-025-00910-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s43587-025-00910-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T01:34:32Z","timestamp":1757208872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s43587-025-00910-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":97,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["910"],"URL":"https:\/\/doi.org\/10.1038\/s43587-025-00910-5","relation":{},"ISSN":["2662-8465"],"issn-type":[{"value":"2662-8465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"assertion":[{"value":"24 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}