The DOI matches its Crossref record; 58 of the 60 references it cites were found in a registry or an index.
Senolytic CAR T cells reverse senescence-associated pathologies
Open accessAbstract
Cellular senescence is characterized by stable cell-cycle arrest and a secretory program that modulates the tissue microenvironment1,2. Physiologically, senescence serves as a tumour-suppressive mechanism that prevents the expansion of premalignant cells3,4 and has a beneficial role in wound-healing responses5,6. Pathologically, the aberrant accumulation of senescent cells generates an inflammatory milieu that leads to chronic tissue damage and contributes to diseases such as liver and lung fibrosis, atherosclerosis, diabetes and osteoarthritis1,7. Accordingly, eliminating senescent cells from damaged tissues in mice ameliorates the symptoms of these pathologies and even promotes longevity1,2,8–10. Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells can be effective senolytic agents. We identify the urokinase-type plasminogen activator receptor (uPAR)11 as a cell-surface protein that is broadly induced during senescence and show that uPAR-specific CAR T cells efficiently ablate senescent cells in vitro and in vivo. CAR T cells that target uPAR extend the survival of mice with lung adenocarcinoma that are treated with a senescence-inducing combination of drugs, and restore tissue homeostasis in mice in which liver fibrosis is induced chemically or by diet. These results establish the therapeutic potential of senolytic CAR T cells for senescence-associated diseases. Chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein that is upregulated on senescent cells, eliminate senescent cells in vitro and in vivo and reduce liver fibrosis in mice.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Certain cell surface proteins tend to be more highly expressed by senescent cells than most other cell types, which prompted development of engineered chimeric antigen receptor (CAR) T cells, vaccines and antibody–drug conjugates targeting these cell surface markers.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [96]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Each of these approaches eliminates senescent cells, although in some cases, activated macrophages and other non-senescent cell types are also affected96–99.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [96]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It was found that anti-uPAR-CAR-T cells were effective in removing senescent cells in vitro and pre-cancerous and malignant cells in mouse models of liver and lung in the presence of potentially toxic.350”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [350]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mice with lung adenocarcinomas were first exposed to a combination of MEK and CDK4/6 inhibitors to induce senescence, and then received uPAR- targeting CAR Tcells to selectively kill those senescent cells, leading to a marked delay in tumour growth 22 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Genome-wide CRISPR screens and transcriptomic profiling have identified several promising SnC-specific targets, with urokinase-type plasminogen activator receptor (uPAR) emerging as a leading candidate63,64”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [63]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“Exciting recent work has demonstrated that senolytic CAR T cell therapy can attenuate senescence-associated diseases226.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [226]
The cited source says what the claim attributes to it.
In the citing paper
“and PLAUR (uPAR) is associated with extracellular remodeling and increased secretion by senescent cells (Amor et al, 2020).”
From Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues (2025) · cites this paper as Amor et al, 2020
The cited source says what the claim attributes to it.
In the citing paper
“Amor et al. (2020) engineered chimeric antigen receptor (CAR) T cells recognizing uPAR, a protein expressed by senescent cells, a strategy that mirrors normal senescence immunosurveillance.”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Amor et al. 2020
The cited source says what the claim attributes to it.
In the citing paper
“these “senolytic CAR T cells” can be used not just as an anticancer therapy, but to treat other senescence-associated disorders, such as nonalcoholic steatohepatitis (NASH) (Amor et al. 2020).”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Amor et al. 2020
The cited source says what the claim attributes to it.
In the citing paper
“Other plasma membrane proteins whose expression has also been reported to change during senescence are receptor- type tyrosine protein phosphatase DEP-1, β 2 -microglobulin, membrane- bound oxidized vimentin, dipeptidyl peptidase 4 and urokinase- type plasminogen activator receptor (uPAR) 22,61,62 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“Moreover, CAR Tcells targeting uPAR on the surface of senescent cells have been developed as promising cell- based senolytics 22 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“chimeric antigen receptor redirected T (CAR-T) cells that target the senescent cell-specific surface molecule uPA receptor [116]”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [116]
The cited source says what the claim attributes to it.
In the citing paper
“In particular, antibodies directed against the glycoprotein NMB (GPNMB) 202 and CAR T cells directed against the receptor uPAR 203 attenuate senescence-associated disease models in mice.”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [203]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Additionally, CXCL16 is upregulated in aging and inflammatory conditions linked to senescence”
From Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues (2025) · cites this paper as Amor et al, 2020
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“transplantation of a small proportion of senescent cells or injection of chimeric antigen receptor (CAR) Tcells with a senescent phenotype accelerated physical dysfunction and reduced lifespan 21,22”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“This approach was successfully validated by a study that used CAR-T to deplete only HSCs that expressed the senescence marker urokinase plasminogen activator receptor (uPAR), thereby improving inflammation and fibrosis (128).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [128]
In the citing paper
“In mouse models, CAR T cells directed against uPAR (urokinase-type plasminogen activator receptor), which is abundantly present on senescent cells, ameliorates experimental liver fibrosis.146”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [146]
In the citing paper
“Moreover, recent studies have shown that uPAR-specific CAR-T cells can effectively eliminate senescent cells in vitro and in vivo and prolong the survival of lung adenocarcinoma mice [127].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [127]
In the citing paper
“Studies have begun to reveal the remarkable heterogeneity of cellular senescence in different tissues, highlighting the importance of cellular senescence markers beyond p16 – including Cdkn1a (p21) [7–10], Cdkn2d (p19) [11], uPAR [12], and glycoprotein non-metastatic melanoma protein B (GPNMB) [13] – and emphasizing the urgent need for a better understanding of senescent cell heterogeneity.”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [12]
In the citing paper
“In another study, urokinase plasminogen activator receptor (uPAR), was identified as a unique senescence marker by comparing differentially expressed genes in bulk RNA-seq datasets of three known mouse models of senescence, and was validated by flow cytometry [12].”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [12]
In the citing paper
“Elimination of uPAR-expressing cells with chimeric antigen receptor (CAR) T cells specifically kills senescent cells both in vivo and in vitro, and extends the lifespan of mice with lung adenocarcinoma [12].”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [12]
In the citing paper
“Similarly, chimeric antigen receptor (CAR) T cells targeting the urokinase-type plasminogen activator receptor (uPAR), reported to be a specific cell surface marker in certain senescent cell populations, effectively ablated senescent cells in vitro and in murine models of lung adenocarcinomas and liver fibrosis (49).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [49]
In the citing paper
“The success of immunotherapies in different forms of cancer have also led to proof-of-concept studies for targeting senescent cells (Amor et al., 2020; Kim et al., 2017).”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Amor et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma’ayan, A. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-128 · Cited by 7,814
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
Self-citationClearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709919 · Cited by 2,688
Self-citationSenolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA
Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., Laberge, R.-M., Vijg, J., Van Steeg, H., Dollé, M. E. T., et al. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.012 · Cited by 2,045
Cited by
Sorted by citations
Hallmarks of Cancer: New Dimensions
Hanahan, D. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1059 · Cited by 9,887
Hallmarks of aging: An expanding universe
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549
Cellular senescence in ageing: from mechanisms to therapeutic opportunities
Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00314-w · Cited by 2,277
Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443
“It was found that anti-uPAR-CAR-T cells were effective in removing senescent cells in vitro and precancerous and malignant cells in mouse models of liver and lung in the presence of potentially toxic.(350) Previously, CAR-T therapy targeting FAP was found to significantly reduce cardiac fibrosis and improve heart func…”
BackgroundSelf-citationAtherosclerosis: Recent developments
Björkegren, J., & Lusis, A. J. (2022) · Cell · doi:10.1016/j.cell.2022.04.004 · Cited by 1,344
Senescence and the SASP: many therapeutic avenues
Birch, J., & Gil, J. (2020) · Genes & Development · doi:10.1101/gad.343129.120 · Cited by 1,177
“Rather than using senolytics, Amor et al. (2020) engineered chimeric antigen receptor (CAR) T cells recognizing uPAR, a protein expressed by senescent cells, a strategy that mirrors normal senescence immunosurveillance.”
BackgroundCellular senescence: the good, the bad and the unknown
Huang, W., Hickson, L. J., Eirin, A., Kirkland, J. L., & Lerman, L. O. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00601-z · Cited by 1,150
Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy
Morris, E. C., Neelapu, S. S., Giavridis, T., & Sadelain, M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00547-6 · Cited by 1,187
Self-citationCellular senescence and senolytics: the path to the clinic
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,134
Immunosenescence: molecular mechanisms and diseases
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01451-2 · Cited by 1,082
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
Hepatic inflammatory responses in liver fibrosis
Hammerich, L., & Tacke, F. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00807-x · Cited by 803
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794
Tumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 836
Mechanisms and therapeutic implications of cellular senescence in osteoarthritis
Coryell, P. R., Diekman, B. O., & Loeser, R. F. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-00533-7 · Cited by 761
CAR immune cells: design principles, resistance and the next generation
Labanieh, L., & Mackall, C. L. (2023) · Nature · doi:10.1038/s41586-023-05707-3 · Cited by 695
A guide to assessing cellular senescence in vitro and in vivo
González‐Gualda, E., Baker, A. G., Fruk, L., & Muñoz‐Espín, D. (2021) · The FEBS Journal · doi:10.1111/febs.15570 · Cited by 645
Cellular senescence: a key therapeutic target in aging and diseases
Zhang, L., Pitcher, L. E., Yousefzadeh, M. J., Niedernhofer, L. J., Robbins, P. D., & Zhu, Y. (2022) · Journal of Clinical Investigation · doi:10.1172/jci158450 · Cited by 631
Immune cell-mediated features of non-alcoholic steatohepatitis
Huby, T., & Gautier, E. L. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00639-3 · Cited by 573
Peiseler, M., Schwabe, R., Hampe, J., Kubes, P., Heikenwälder, M., & Tacke, F. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.012 · Cited by 564
CAR T therapy beyond cancer: the evolution of a living drug
Baker, D. J., Arany, Z. P., Baur, J. A., Epstein, J. A., & June, C. H. (2023) · Nature · doi:10.1038/s41586-023-06243-w · Cited by 546
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510
Strategies for targeting senescent cells in human disease
Gasek, N. S., Kuchel, G. A., Kirkland, J. L., & Xu, M. (2021) · Nature Aging · doi:10.1038/s43587-021-00121-8 · Cited by 501
The aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500
From bench to bedside: the history and progress of CAR T cell therapy
Mitra, A., Barua, A., Huang, L., Ganguly, S., Feng, Q. F., & He, B. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1188049 · Cited by 526
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 450
Metabolic reprogramming in liver fibrosis
Horn, P., & Tacke, F. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.05.003 · Cited by 432
Immune ageing at single-cell resolution
Mogilenko, D. A., Shchukina, I., & Artyomov, M. N. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00646-4 · Cited by 396
Redox regulation: mechanisms, biology and therapeutic targets in diseases
Li, B., Ming, H., Qin, S., Nice, E. C., Dong, J., Du, Z., & Huang, C. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02095-6 · Cited by 389
Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Marín, I., Boix, O., García-Garijo, A., Sirois, I., Caballé, A., Zarzuela, E., Ruano, I., Attolini, C. S., Prats, N., Lopez-Dominguez, J. A., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0523 · Cited by 365
Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
Llovet, J. M., Willoughby, C. E., Singal, A. G., Greten, T. F., Heikenwälder, M., El-Serag, H. B., Finn, R. S., & Friedman, S. L. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00754-7 · Cited by 354
Self-citationTherapy-Induced Senescence: Opportunities to Improve Anticancer Therapy
Prasanna, P. G. S., Citrin, D. E., Hildesheim, J., Ahmed, M. M., Venkatachalam, S., Riscuta, G., Xi, D., Zheng, G., van Deursen, J., Goronzy, J. J., et al. (2021) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djab064 · Cited by 359
Self-citationThe flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice
Xu, Q., Fu, Q., Li, Z., Liu, H., Wang, Y., Lin, X., He, R., Zhang, X., Ju, Z., Campisi, J., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00491-8 · Cited by 341
Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span
Robbins, P. D., Jurk, D., Khosla, S., Kirkland, J. L., LeBrasseur, N. K., Miller, J. D., Passos, J. F., Pignolo, R. J., Tchkonia, T., & Niedernhofer, L. J. (2021) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-050120-105018 · Cited by 360
Co-opting signalling molecules enables logic-gated control of CAR T cells
Tousley, A. M., Rotiroti, M. C., Labanieh, L., Rysavy, L. W., Kim, W., Lareau, C. A., Sotillo, E., Weber, E. W., Rietberg, S. P., Dalton, G. N., et al. (2023) · Nature · doi:10.1038/s41586-023-05778-2 · Cited by 350
Xiao, X., Huang, S., Chen, S., Wang, Y., Sun, Q., Xu, X., & Li, Y. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02148-6 · Cited by 347
An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH
Tacke, F., Puengel, T., Loomba, R., & Friedman, S. L. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.038 · Cited by 321
Self-citationEpithelial–immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis
Verstappen, G. M. P. J., Pringle, S. A., Bootsma, H., & Kroese, F. G. M. (2021) · Nature Reviews Rheumatology · doi:10.1038/s41584-021-00605-2 · Cited by 322
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 323
Inflammation-Induced Tumorigenesis and Metastasis
Hibino, S., Kawazoe, T., Kasahara, H., Itoh, S., Ishimoto, T., Sakata‐Yanagimoto, M., & Taniguchi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115421 · Cited by 319
The heterogeneity of cellular senescence: insights at the single-cell level
Cohn, R. L., Gasek, N. S., Kuchel, G. A., & Xu, M. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.04.011 · Cited by 294
Cellular senescence and SASP in tumor progression and therapeutic opportunities
Dong, Z., Luo, Y., Yuan, Z., Tian, Y., Jin, T., & Feng, X. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02096-7 · Cited by 315
Immune Cells and Immunotherapy for Cardiac Injury and Repair
Rurik, J. G., Aghajanian, H. K., & Epstein, J. A. (2021) · Circulation Research · doi:10.1161/circresaha.121.318005 · Cited by 275
Rasmussen, L. J. H., Petersen, J. E. V., & Eugen‐Olsen, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.780641 · Cited by 261
The role of T cells in age-related diseases
Carrasco, E., Heras, M. M. G. D. L., Gabandé‐Rodríguez, E., Desdín-Micó, G., Aranda, J. F., & Mittelbrunn, M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00557-4 · Cited by 250
Cancer and Aging: Two Tightly Interconnected Biological Processes
Berben, L., Floris, G., Wildiers, H. P. M. W., & Hatse, S. (2021) · Cancers · doi:10.3390/cancers13061400 · Cited by 253
Amor, C., Fernández-Maestre, I., Chowdhury, S., Ho, Y.-J., Nadella, S., Graham, C., Carrasco, S. E., Nnuji-John, E., Feucht, J., Hinterleitner, C., et al. (2024) · Nature Aging · doi:10.1038/s43587-023-00560-5 · Cited by 228
Self-citationEngineered CAR-Macrophages as Adoptive Immunotherapies for Solid Tumors
Sloas, D. C., Gill, S. I., & Klichinsky, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.783305 · Cited by 246
Zhu, J., Yang, S., Qi, Y., Gong, Z., Zhang, H., Liang, K., Shen, P., Huang, Y.-Y., Zhang, Z., Ye, W., et al. (2022) · Science Advances · doi:10.1126/sciadv.abk0011 · Cited by 242
Cellular senescence at the crossroads of inflammation and Alzheimer's disease
Guerrero, A., De Strooper, B., & Arancibia-Cárcamo, I. L. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.06.007 · Cited by 236
Gerhardt, L. M. S., Liu, J., Koppitch, K. A., Cippà, P. E., & McMahon, A. P. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2026684118 · Cited by 237
Targeting immune dysfunction in aging
Borgoni, S., Kudryashova, K. S., Burka, K., & de Magalhães, J. P. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101410 · Cited by 232
Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions
Brauning, A., Rae, M., Zhu, G., Fulton, E., Admasu, T. D., Stolzing, A., & Sharma, A. (2022) · Cells · doi:10.3390/cells11061017 · Cited by 215
NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates
Yang, D., Sun, B., Li, S., Wei, W., Liu, X., Cui, X., Zhang, X., Liu, N., Yan, L., Deng, Y., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.add1951 · Cited by 217
Senescence in osteoarthritis: from mechanism to potential treatment
Liu, Y., Zhang, Z., Li, T., Xu, H., & Zhang, H. (2022) · Arthritis Research & Therapy · doi:10.1186/s13075-022-02859-x · Cited by 210
Fibrosis in IBD: from pathogenesis to therapeutic targets
Rieder, F., Mukherjee, P. K., Massey, W. J., Wang, Y., & Fiocchi, C. (2024) · Gut · doi:10.1136/gutjnl-2023-329963 · Cited by 218
Montégut, L., López-Otín, C., & Kroemer, G. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02020-z · Cited by 222
Han, Y., & Kim, S. Y. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00906-w · Cited by 201
Roles of extracellular vesicles in the aging microenvironment and age‐related diseases
Yin, Y., Chen, H., Wang, Y., Zhang, L., & Wang, X. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12154 · Cited by 205
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 197
Cellular senescence in cancer: from mechanisms to detection
Ou, H., Hoffmann, R. J., González‐López, C., Doherty, G. J., Korkola, J. E., & Muñoz‐Espín, D. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12807 · Cited by 208
From concept to cure: The evolution of CAR-T cell therapy
Patel, K. K., Tariveranmoshabad, M., Kadu, S., Shobaki, N., & June, C. H. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.03.005 · Cited by 211
Selman, M., & Pardo, A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101393 · Cited by 211
Natural killer cells: a promising immunotherapy for cancer
Chu, J., Gao, F., Yan, M., Zhao, S., Yan, Z., Shi, B., & Liu, Y. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03437-0 · Cited by 194
Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives
Zhang, M., Salas, S. S., Damba, T., Borghesan, M., Demaria, M., & Moshage, H. J. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111572 · Cited by 192
Cellular senescence and the tumour microenvironment
Takasugi, M., Yoshida, Y., & Ohtani, N. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13268 · Cited by 190
Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs
Kudlová, N., Sanctis, J. B. D., & Hajdúch, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084168 · Cited by 186
Cellular senescence in knee osteoarthritis: molecular mechanisms and therapeutic implications
Xie, J., Wang, Y., Lu, L., Liu, L., Yu, X., & Pei, F. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101413 · Cited by 178
Chambers, C. R., Ritchie, S., Pereira, B., & Timpson, P. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13042 · Cited by 182
Basu, A. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107943 · Cited by 171
Cellular Senescence: From Mechanisms to Current Biomarkers and Senotherapies
Lucas, V., Cavadas, C., & Aveleira, C. A. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000622 · Cited by 172
The Role of Oxidative Stress in Cardiovascular Aging and Cardiovascular Diseases
Izzo, C., Vitillo, P., Pietro, P. D., Visco, V., Strianese, A., Virtuoso, N., Ciccarelli, M., Galasso, G., Carrizzo, A., & Vecchione, C. (2021) · Life · doi:10.3390/life11010060 · Cited by 177
Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development
Hu, L., Li, H., Zi, M., Li, W., Liu, J., Yang, Y., Zhou, D., Kong, Q., Zhang, Y., & He, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.822816 · Cited by 174
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158
Self-citationFriend or foe? The elusive role of hepatic stellate cells in liver cancer
Cogliati, B., Yashaswini, C. N., Wang, S., Sia, D., & Friedman, S. L. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00821-z · Cited by 159
Self-citationFibrosis Regression After Eradication of Hepatitis C Virus: From Bench to Bedside
Rockey, D. C., & Friedman, S. L. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.09.065 · Cited by 157
Self-citationCardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis
Ko, T., Nomura, S., Yamada, S., Fujita, K., Fujita, T., Satoh, M., Oka, C., Katoh, M., Ito, M., Katagiri, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30630-y · Cited by 164
In vivo chimeric antigen receptor (CAR)-T cell therapy
Bot, A., Scharenberg, A. M., Friedman, K. M., Guey, L. T., Hofmeister, R., Andorko, J. I., Klichinsky, M., Neumann, F., Shah, J. V., Swayer, A. J., et al. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01291-5 · Cited by 172
Lelarge, V., Capelle, R., Oger, F., Mathieu, T., & Le Calvé, B. (2024) · npj Aging · doi:10.1038/s41514-024-00138-4 · Cited by 140
The role of cellular senescence and SASP in tumour microenvironment
Takasugi, M., Yoshida, Y., Hara, E., & Ohtani, N. (2023) · The FEBS Journal · doi:10.1111/febs.16381 · Cited by 144
Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Yaeger, R., Mezzadra, R., Sinopoli, J., Bian, Y., Marasco, M., Kaplun, E., Gao, Y., Zhao, H., Paula, A. D. C., Zhu, Y., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0405 · Cited by 144
Self-citationBoyajian, J. L., Ghebretatios, M., Schaly, S., Islam, P., & Prakash, S. (2021) · Nutrients · doi:10.3390/nu13124550 · Cited by 115
Stress, epigenetics, and aging: Unraveling the intricate crosstalk
Wu, Z., Qu, J. T., Zhang, W., & Liu, G. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.10.006 · Cited by 145
When dormancy fuels tumour relapse
Santos-de-Frutos, K., & Djouder, N. (2021) · Communications Biology · doi:10.1038/s42003-021-02257-0 · Cited by 153
Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities
Liu, Y., Zhou, X., & Wang, X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01134-x · Cited by 142
Senescence and the tumor-immune landscape: Implications for cancer immunotherapy
Chibaya, L., Snyder, J. T., & Ruscetti, M. A. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.02.005 · Cited by 146
Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma
Salam, R., Saliou, A., Bielle, F., Bertrand, M., Antoniewski, C., Carpentier, C., Alentorn, A., Capelle, L., Sanson, M., Huillard, E., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36124-9 · Cited by 132
Upregulation of PD-L1 in Senescence and Aging
Onorati, A., Havas, A. P., Lin, B., Rajagopal, J., Sen, P., Adams, P. D., & Dou, Z. (2022) · Molecular and Cellular Biology · doi:10.1128/mcb.00171-22 · Cited by 131
Theranostic cells: emerging clinical applications of synthetic biology
McNerney, M. P., Doiron, K. E., Ng, T. L., Chang, T. Z., & Silver, P. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00383-3 · Cited by 131
Colucci, M., Sarill, M., Maddalena, M., Valdata, A., Troiani, M., Massarotti, M., Bolis, M., Bressan, S., Kohl, A., Robesti, D., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.05.015 · Cited by 143
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death
Bu, L.-L., Yuan, H., Xie, L., Guo, M.-H., Liao, D., & Zheng, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015160 · Cited by 133
CAR-based therapies: opportunities for immuno-medicine beyond cancer
Aghajanian, H. K., Rurik, J. G., & Epstein, J. A. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00537-5 · Cited by 130
Senolytics for Cancer Therapy: Is All that Glitters Really Gold?
Carpenter, V. J., Saleh, T., & Gewirtz, D. A. (2021) · Cancers · doi:10.3390/cancers13040723 · Cited by 124
Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer
Zhai, B., Tian, H., Sun, J., Zou, J., Zhang, X., Cheng, J., Shi, Y., Fan, Y. B., & Guo, D. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03329-3 · Cited by 123
Belle, J. I., Sen, D., Baer, J. M., Liu, X., Lander, V. E., Ye, J., Sells, B. E., Knolhoff, B. L., Ahmad, F. F., Kang, L., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0428 · Cited by 124
SenNet Consortium, Writing Group, Lee, P. J., Benz, C. C., Blood, P., Börner, K., Campisi, J., Chen, F., Daldrup-Link, H., De Jager, P., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00326-5 · Cited by 122
Type 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging
Zhou, Z., Yao, J., Wu, D., Huang, X., Wang, Y., Li, X., Lu, Q., & Qiu, Y. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.001 · Cited by 122
Self-citationCellular senescence: Neither irreversible nor reversible
Reimann, M., Lee, S., & Schmitt, C. A. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20232136 · Cited by 125
Metadata
- Authors
- Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., Kulick, A., Houlihan, S., Peerschke, E., Friedman, S. L., Ponomarev, V., Piersigilli, A., Sadelain, M., & Lowe, S. W.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Sadelain, Michel
- Lowe, Scott W.
- ORCID
- Venue
- Nature
- Published
- 2020-06-17
- Volume
- 583
- Issue
- 7814
- Pages
- 127-132
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7583560
- OpenAlex
- W3036603151
- Semantic Scholar
- 04e18a651e78de49d44a74b1db3d968208b4c3a1
- Cited by
- 1,098
- References
- 60
- Citations by year
- 2026: 194 · 2025: 236 · 2024: 208 · 2023: 147 · 2022: 135 · 2021: 131 · 2020: 45
- FWCI
- 68.89
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-02-21)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (U54OD020355)
- National Institute on Aging (AG065396, R56AG016379, R01AG016379, R01AG065396)
- National Cancer Institute (P01CA129243, P30CA008748)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056621)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, chimeric antigen receptor T cells, urokinase-type plasminogen activator receptor, liver fibrosis, lung adenocarcinoma, senescence-associated secretory phenotype, tissue homeostasis
- MeSH terms
- Receptors, Chimeric Antigen, Adenocarcinoma, Aging, Animals, Carbon Tetrachloride, Female, Humans, Liver Cirrhosis, Longevity, Lung Neoplasms, Male, Receptors, Cell Surface, Rejuvenation, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Cellular Senescence, Mice, Receptors, Urokinase Plasminogen Activator, Heterografts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
