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Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians
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Abstract
Supercentenarians, people who have reached 110 y of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from 7 supercentenarians and 5 younger controls. We identified a marked increase of cytotoxic CD4 T cells (CD4 cytotoxic T lymphocytes [CTLs]) as a signature of supercentenarians. Furthermore, single-cell T cell receptor sequencing of 2 supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15 to 35% of the entire CD4 T cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Indeed, CD4 CTLs extracted from supercentenarians produced IFN-γ and TNF-α upon ex vivo stimulation. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.
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“Studies have shown lower levels of B cells, similar numbers of T cells, and a higher percentage of cytotoxic T cells in the peripheral blood of supercentenarians.318”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [318]
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“CD8+ cytotoxic T cells directly eradicate target cells using cytotoxic molecules via recognizing MHC I molecules within nearly all cells [127].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [127]
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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
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Massively parallel digital transcriptional profiling of single cells
Zheng, G. X. Y., Terry, J. M., Belgrader, P., Ryvkin, P., Bent, Z. W., Wilson, R., Ziraldo, S. B., Wheeler, T. D., McDermott, G. P., Zhu, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14049 · Cited by 7,353
Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing
Zheng, C., Zheng, L., Yoo, J.-K., Guo, H., Zhang, Y., Guo, X., Kang, B., Hu, R., Huang, J. Y., Zhang, Q., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.035 · Cited by 2,152
Single-cell mRNA quantification and differential analysis with Census
Qiu, X., Hill, A. J., Packer, J. S., Lin, D., Ma, Y.-A., & Trapnell, C. (2017) · Nature Methods · doi:10.1038/nmeth.4150 · Cited by 1,904
Single-cell RNA sequencing to explore immune cell heterogeneity
Papalexi, E., & Satija, R. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.76 · Cited by 1,806
HIV Infection, Inflammation, Immunosenescence, and Aging
Deeks, S. G. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-042909-093756 · Cited by 1,349
Cell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · cited 1×
“5 stem cells in bone marrow exhibit a myeloid-biased differentiation potential (12, 13), which 70 causes changes in the cell population of peripheral blood.”
BackgroundSingle-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer
Chung, W., Eum, H. H., Lee, H.-O., Lee, K.-M., Lee, H.-B., Kim, K.-T., Ryu, H. S., Kim, S., Lee, J. E., Park, Y. H., et al. (2017) · Nature Communications · doi:10.1038/ncomms15081 · Cited by 992 · cited 1×
“These methods have been applied to various subjects such as finding signatures of aging in the human pancreas (22), observing infiltrating T cells in tumors (23, 24), and characterizing diversity of cell types during brain development (25).”
MethodHuman bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116110108 · Cited by 991
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Items 101–200 of 342
The multiomics blueprint of the individual with the most extreme lifespan
Santos-Pujol, E., Noguera‐Castells, A., Casado-Peláez, M., García-Prieto, C. A., Vasallo, C., Campillo‐Marcos, I., Quero-Dotor, C., Crespo-García, E., Bueno-Costa, A., Setién, F., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102368 · Cited by 26
Senescence and Type 2 Diabetic Cardiomyopathy: How Young Can You Die of Old Age?
Henson, S. M., & Aksentijević, D. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.716517 · Cited by 23
Tanemoto, S., Sujino, T., Miyamoto, K., Moody, J., Yoshimatsu, Y., Ando, Y., Koya, I., Harada, Y., Tojo, A. O., Ono, K., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.977117 · Cited by 22
Self-citationEschke, M., Moore, P. F., Chang, H., Alber, G., & Keller, S. M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1123366 · Cited by 22
Ligotti, M. E., Accardi, G., Aiello, A., Calabrò, A., Caruso, C., Corsale, A. M., Dieli, F., Simone, M. D., Meraviglia, S., & Candore, G. (2023) · Clinical & Experimental Immunology · doi:10.1093/cei/uxad132 · Cited by 22
Zhong, J., Ding, R., Jiang, H., Li, L., Wan, J., Feng, X., Chen, M., Peng, L., Li, X., Lin, J., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1081889 · Cited by 25
The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation
Acton, R., Yuan, W., Gao, F., Xia, Y., Bourne, E., Wozniak, E., Bell, J. T., Lillycrop, K. A., Wang, J., Dennison, E. M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22639-6 · Cited by 21
Yan, S., Si, Y., Zhou, W., Cheng, R., Wang, P., Wang, D., Ding, W., Shi, W., Jiang, Q., Yang, F., et al. (2023) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2023.106801 · Cited by 24
Ligotti, M. E., Accardi, G., Aiello, A., Calabrò, A., Caruso, C., Corsale, A. M., Dieli, F., Simone, M. D., Meraviglia, S., & Candore, G. (2023) · Translational Medicine UniSa · doi:10.37825/2239-9747.1041 · Cited by 21
Meta-epigenetic shifts in T cell aging and aging-related dysfunction
Rousseau, L., Hajdu, K. L., & Ho, P. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01146-6 · Cited by 21
Burchill, M. A., Salomon, M. P., Golden‐Mason, L., Wieland, A. C., Maretti-Mira, A. C., Gale, M., & Rosen, H. R. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009799 · Cited by 20
Hayashi, R., Nagato, T., Kumai, T., Ohara, K., Ohara, M., Ohkuri, T., Hirata‐Nozaki, Y., Harabuchi, S., Kosaka, A., Nagata, M., et al. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1856545 · Cited by 20
Neurologic and Neuroscientific Evidence in Aged COVID-19 Patients
Mainali, S., & Darsie, M. E. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.648662 · Cited by 21
Scaglione, A., Opp, S., Hurtado, A. M., Lin, Z., Pampeno, C., Noval, M. G., Thannickal, S. A., Stapleford, K. A., & Meruelo, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.719077 · Cited by 20
Understanding T cell aging to improve anti-viral immunity
Zhang, H., Weyand, C. M., Goronzy, J. J., & Gustafson, C. E. (2021) · Current Opinion in Virology · doi:10.1016/j.coviro.2021.09.017 · Cited by 18
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Elyahu, Y., Feygin, I., Eremenko, E., Pinkas, N., Zemer, A., Shicht, A., Berner, O., Avigdory-Meiri, R., Nemirovsky, A., Reshef, K., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00953-8 · Cited by 19
Immunity and lifespan: answering long-standing questions with comparative genomics
O’Connor, E., & Cornwallis, C. K. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.02.014 · Cited by 19
Longevity, Centenarians and Modified Cellular Proteodynamics
Frankowska, N., Bryl, E., Fülöp, T., & Witkowski, J. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032888 · Cited by 20
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Accardi, G., Aiello, A., Aprile, S., Caldarella, R., Cammarata, G., Carru, C., Caruso, C., Ciaccio, M., Colomba, P., Galimberti, D., et al. (2020) · Rejuvenation Research · doi:10.1089/rej.2019.2299 · Cited by 19
Dynamic clonal hematopoiesis and functional T-cell immunity in a supercentenarian
van den Akker, E. B., Makrodimitris, S., Hulsman, M., Brugman, M. H., Nikolić, T., Bradley, T., Waisfisz, Q., Baas, F., Jakobs, M. E., de Jong, D., et al. (2020) · Leukemia · doi:10.1038/s41375-020-01086-0 · Cited by 19
Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets
Lai, L., Ran, S., Li, Y., Cui, J., Zhang, X., Yu, J., Zou, Y., Cheng, Z., Xia, J., & Wu, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02533-z · Cited by 24
Guo, X., Ning, J., Chen, Y., Liu, G., Zhao, L., Fan, Y., & Sun, S. (2023) · Briefings in Functional Genomics · doi:10.1093/bfgp/elad011 · Cited by 19
Cordiano, R., Caserta, S., Minciullo, P. L., Allegra, A., & Gangemi, S. (2025) · Molecules · doi:10.3390/molecules30061251 · Cited by 23
Immune system aging and the aging-related diseases in the COVID-19 era
Witkowski, J. M. (2022) · Immunology Letters · doi:10.1016/j.imlet.2022.01.005 · Cited by 20
Mo, S., Shi, C., Cai, Y., Xu, M., Xu, H., Xu, Y., Zhang, K., Zhang, Y., Liu, J., Che, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1387808 · Cited by 18
Repertoire-scale measures of antigen binding
Arora, R., & Arnaout, R. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2203505119 · Cited by 16
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de Castro, M. V., Silva, M. V. R., Naslavsky, M. S., Scliar, M. O., Nunes, K., Passos‐Bueno, M. R., Castelli, E. C., Magawa, J. Y., Adami, F. L., Moretti, A. I. S., et al. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00310-y · Cited by 18
Jinna, N., Rida, P. C. G., Su, T., Gong, Z., Yao, S., LaBarge, M. A., Natarajan, R. D., Jovanović‐Talisman, T., Ambrosone, C. B., & Seewaldt, V. L. (2022) · Cells · doi:10.3390/cells11233818 · Cited by 21
Liu, J., Si, H., Huang, D., Lu, D., Zou, S., Qi, D., Pei, X., Huang, S., & Li, Z. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.12.18 · Cited by 17
Xu, Y., Wang, Z., Li, S., Su, J., Gao, L., Ou, J., Lin, Z., Luo, O. J., Xiao, C., & Chen, G. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2695-x · Cited by 20
Xu, C., Yang, J., Kosters, A., Babcock, B. R., Qiu, P., & Ghosn, E. (2022) · iScience · doi:10.1016/j.isci.2022.105123 · Cited by 18
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Alayoubi, Y., Bentsen, M. S., & Looso, M. (2024) · Scientific Reports · doi:10.1038/s41598-024-66381-7 · Cited by 18
Accardi, G., Calabrò, A., Caldarella, R., Caruso, C., Ciaccio, M., Simone, M. D., Ligotti, M. E., Meraviglia, S., Zarcone, R., Candore, G., et al. (2024) · Biology · doi:10.3390/biology13121010 · Cited by 15
Dong, C., Miao, Y., Zhao, R. Z., Yang, M., Guo, A., Xue, Z., Li, T., Zhang, Q., Bao, Y., Shen, C., et al. (2022) · Advanced Science · doi:10.1002/advs.202204849 · Cited by 16
Chen, Z., Zhang, M., Liu, Y., Chen, Z., Wang, L., Wang, W., Wang, J., He, M., Shi, B., & Wang, Y. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-03926-w · Cited by 16
Franzin, R., Stasi, A., Castellano, G., & Gesualdo, L. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1507-2_6 · Cited by 14
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Zhang, W., Huang, Q., Kang, Y., Li, H., & Tan, G. (2022) · Aging and Disease · doi:10.14336/ad.2022.1108 · Cited by 16
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Joachim, A., Aussel, R., Gelard, L., Zhang, F., Mori, D., Grégoire, C., Villazala‐Merino, S., Gaya, M., Liang, Y., Malissen, M., et al. (2023) · The Journal of Experimental Medicine · doi:10.1084/jem.20231028 · Cited by 13
Wang, H., Xiao, F., Gao, Z., Guo, L., Yang, L., Li, G., & Kong, Q. (2024) · Aging Cell · doi:10.1111/acel.14163 · Cited by 15
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Li, Y., Wang, Q., Xuan, Y., Zhao, J., Li, J., Tian, Y., Chen, G., & Tan, F. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102530 · Cited by 16
Wang, Q., Che, N., Lu, C., Sun, X., Wang, Y., Wang, Q., Tan, W., Zhou, L., Zhang, X., Xu, D., et al. (2021) · Arthritis Research & Therapy · doi:10.1186/s13075-021-02632-6 · Cited by 15
Trzupek, D., Lee, M., Hamey, F., Wicker, L. S., Todd, J. A., & Ferreira, R. C. (2022) · Wellcome Open Research · doi:10.12688/wellcomeopenres.16883.2 · Cited by 16
Liu, G., Antoun, E., Fries, A., Yao, X., Yin, Z., Dong, D., Wang, W., Wing, P. A. C., Dejnirattisa, W., Supasa, P., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63711-9 · Cited by 14
Song, Z., Chen, B., Tsai, C.-H., Wu, D., Liu, E., Hawkins, I. S., Phan, A., Auman, J. T., Tao, Y., & Mei, H. (2022) · Cells · doi:10.3390/cells11131983 · Cited by 14
Urban, B. C., Gonçalves, A. N. A., Loukov, D., Passos, F. M., Reiné, J., Gonzalez‐Dias, P., Solórzano, C., Mitsi, E., Nikolaou, E., O’Connor, D., et al. (2024) · Mucosal Immunology · doi:10.1016/j.mucimm.2024.06.010 · Cited by 14
Gao, C., Wang, S., Xie, X., Ramadori, P., Li, X., Liu, X., Ding, X., Liang, J., Xu, B., Feng, Y., et al. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101411 · Cited by 17
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Summer, S., Borrell-Pagés, M., Bruno, R. M., Climie, R. E., Δίπλα, Κ., Dogan, A., Eruslanova, K. A., Fraenkel, E., Mattace-Raso, F. U. S., Pugh, C. J. A., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01467-8 · Cited by 16
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Adachi, T., Kainuma, K., Asano, K., Amagai, M., Arai, H., Ishii, K. J., Ito, K., Uchio, E., Ebisawa, M., Okano, M., et al. (2020) · Allergology International · doi:10.1016/j.alit.2020.04.006 · Cited by 14
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Iqbal, H., & Rhee, D. (2025) · Journal of Ginseng Research · doi:10.1016/j.jgr.2025.05.005 · Cited by 16
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Plaza‐Florido, A., Carrera‐Bastos, P., Pérez‐Prieto, I., Fiuza‐Luces, C., Radom‐Aizik, S., Cruz, B. D. P., Franceschi, C., López‐Soto, A., López-Otı́n, C., & Lucía, A. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-026-01291-5 · Cited by 13
de Fàbregues, O., Sellés, M. C., Ramos-Vicente, D., Roch, G., Vila, M., & Bové, J. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106308 · Cited by 12
Cytotoxic CD4+ T Cells Are Induced during Infection with Chlamydia trachomatis
Olivas, J., Nogueira, C., Helble, J. D., & Starnbach, M. N. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2300131 · Cited by 13
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Huang, L., Zhang, M., Bai, D., & Qu, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1465006 · Cited by 13
Senescence-associated T cells in immunosenescence and diseases
Fukushima, Y., Ueno, R., Minato, N., & Hattori, M. (2024) · International Immunology · doi:10.1093/intimm/dxae056 · Cited by 14
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Liu, X., Kamatani, Y., & Terao, C. (2021) · Journal of Human Genetics · doi:10.1038/s10038-021-00964-4 · Cited by 13
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Chebly, A., Khalil, C., Kuzyk, A. C., Beylot-Barry, M., & Chevret, E. (2023) · Biogerontology · doi:10.1007/s10522-023-10075-6 · Cited by 13
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Grigorescu, A., Riza, A., Streață, I., & Netea, M. G. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00153.2025 · Cited by 16
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Li, H., Liu, H., Liu, Y., Wang, X., Yu, S., Huang, H., Shen, X., Zhang, Q., Hong, N., & Jin, W. (2023) · iScience · doi:10.1016/j.isci.2023.107588 · Cited by 12
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Saenz‐Antoñanzas, A., Muñoz‐Culla, M., Rigo, P., Ruiz‐Barreiro, L., Moreno‐Valladares, M., Alberro, A., Cruces‐Salguero, S., Arroyo‐Izaga, M., Arranz, A. M., Otaegui, D., et al. (2024) · Aging Cell · doi:10.1111/acel.14201 · Cited by 11
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Wu, D., Bi, X., Li, P., Xu, D., Qiu, J., Li, K., Zheng, S., & Chow, H. (2023) · Aging Cell · doi:10.1111/acel.13810 · Cited by 11
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Tsai, Y.-T., Seymen, N., Thompson, I. R., Zou, X., Mumtaz, W., Gerlevik, S., Mufti, G. J., & Karimi, M. M. (2024) · eLife · doi:10.7554/elife.96575 · Cited by 14
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Song, N., Elbahnasawy, M. A., & Weng, N. (2025) · The Journal of Immunology · doi:10.1093/jimmun/vkae033 · Cited by 11
Verma, M., Randhawa, S., Bathla, M., Teji, N., & Acharya, A. (2025) · Journal of Materials Chemistry B · doi:10.1039/d4tb02409e · Cited by 13
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Nikolaou, C., Mühle, K., Schlickeiser, S., Japp, A. S., Matzmohr, N., Kunkel, D., Frentsch, M., & Thiel, A. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00230-3 · Cited by 11
Maquet, C., Baiwir, J., Loos, P., Rodriguez-Rodriguez, L., Javaux, J., Sandor, R., Perin, F., Fallon, P. G., Mack, M., Cataldo, D. D., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abn3240 · Cited by 11
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Zhang, C., Ren, T., Zhao, X., Su, Y., Wang, Q., Zhang, T., He, B., Chen, Y., Wu, L., Sun, L., et al. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00479-4 · Cited by 10
Wang, Y., Zhang, Y., Gong, G., Liu, Q., Li, L., Zhang, M., Shen, S., Wang, R., Wu, J., & Xu, W. (2024) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2024.112011 · Cited by 10
Wang, B., Zhang, Z., Ouyang, Q., Zhang, M., Duan, M., Hu, H., Zhang, Q., Jin, X., Zhang, J., Luo, Q., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.105922 · Cited by 10
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Dobreva, T., Brown, D. A., Park, J. H., & Thomson, M. W. (2020) · Scientific Reports · doi:10.1038/s41598-020-77073-3 · Cited by 10
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Strzelecka, P. M., & Damm, F. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.047340 · Cited by 10
Accardi, G., Aiello, A., Aprile, S., Calabrò, A., Caldarella, R., Ciaccio, M., Caruso, C., Dieli, F., Ligotti, M. E., Meraviglia, S., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12247591 · Cited by 9
Elahee, M., Mueller, A. A., Wang, R., Marks, K. E., Sasaki, T., Cao, Y., Fava, A., Dellaripa, P. F., Boin, F., & Rao, D. A. (2024) · ACR Open Rheumatology · doi:10.1002/acr2.11671 · Cited by 9
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Decoding immune aging at single-cell resolution
Wang, Y., Ke, D., Chen, Y., Zhang, C., Liu, W., Chen, L., & Pu, J. (2025) · Trends in Immunology · doi:10.1016/j.it.2025.09.001 · Cited by 11
Choi, S. M., Park, H. J., Choi, E. A., Jung, K. C., & Lee, J. I. (2022) · Scientific Reports · doi:10.1038/s41598-022-18340-3 · Cited by 9
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Hu, Y., He, L., & Long, H. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103957 · Cited by 10
Osório, T. G., Pavesi, E., Abou‐El‐Ardat, K., Qureshi, N., Cassidy, L., John, T. L. S., Sirotin, N., & Piechowski‐Jóźwiak, B. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1656727 · Cited by 11
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Klinedinst, B. S., Kharate, M., Mohammadiarvejeh, P., Fili, M., Pollpeter, A., Larsen, B. A., Moody, S. N., Wang, Q., Allenspach, K., Mochel, J. P., et al. (2023) · GeroScience · doi:10.1007/s11357-023-00765-x · Cited by 9
Shohdy, K. S., Almeldin, D. S., Ghaly, R., Kassem, L. M. H., & Pagani, O. (2021) · Journal of Immunotherapy and Precision Oncology · doi:10.36401/jipo-21-15 · Cited by 8
Enssle, J. C., Campe, J., Moter, A., Voit, I., Geßner, A., Yu, W., Wolf, S., Steffen, B., Serve, H. L., Bremm, M., et al. (2023) · Leukemia · doi:10.1038/s41375-023-02070-0 · Cited by 8
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Kock, K. H., Tan, L. M., Han, K. Y., Ando, Y., Jevapatarakul, D., Chatterjee, A., Lin, Q. X. X., Buyamin, E. V., Sonthalia, R., Rajagopalan, D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.30.601119 · Cited by 8
Self-citationZhang, S., Jahanbani, F., Chander, V., Kjellberg, M., Liu, M., Glass, K. A., Iu, D. S., Ahmed, F., Li, H., Maynard, R. D., et al. (2025) · medRxiv · doi:10.1101/2025.04.15.25325899 · Cited by 9
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Fernández-Maestre, I., Harris, A. S., & Amor, C. (2025) · Genes & Development · doi:10.1101/gad.352644.125 · Cited by 8
Olwenyi, O. A., Johnson, S. D., Pandey, K., Thurman, M., Acharya, A., Buch, S. J., Fox, H. S., Podany, A. T., Fletcher, C. V., & Byrareddy, S. N. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.734871 · Cited by 7
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Hernandez, A. M., Mossman, J. A., Toapanta, F. R., Previte, D. M., Ross, T. M., & Nau, G. J. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00286-9 · Cited by 7
Dressman, D., Buttrick, T., Cimpean, M., Bennett, D. A., Menon, V., Bradshaw, E. M., Vardarajan, B. N., & Elyaman, W. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac126 · Cited by 7
Yonemoto, Y., Nemoto, Y., Morikawa, R., Shibayama, N., Oshima, S., Nagaishi, T., Mizutani, T., Ito, G., Fujii, S., & Okamoto, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1340048 · Cited by 6
Akiyama, M., Yoshimoto, K., & Kaneko, Y. (2023) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/kfsd65 · Cited by 7
Nathan, A., Beynor, J. I., Baglaenko, Y., Suliman, S., Ishigaki, K., Asgari, S., Huang, C.-C., Luo, Y., Zhang, Z., Lopez, K., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.23.057828 · Cited by 7
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Lacaud, M., Bouzidi, H., Petit, M., Breckler, M., Lemeiter, D., Sigaux, J., Rivière, É., Semerano, L., Boissier, M., Bessis, N., et al. (2025) · Arthritis & Rheumatology · doi:10.1002/art.43124 · Cited by 6
Bergero, G., Mazzocco, Y. L., Rosso, S. D., Liu, R., Gallardo, Z. M. C., Robson, S. C., Rottenberg, M. E., & Aoki, M. P. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186785 · Cited by 6
Metadata
- Authors
- Hashimoto, K., Kouno, T., Ikawa, T., Hayatsu, N., Miyajima, Y., Yabukami, H., Terooatea, T., Sasaki, T., Suzuki, T., Valentine, M., Pascarella, G., Okazaki, Y., Suzuki, H., Shin, J. W., Minoda, A., Taniuchi, I., Okano, H., Arai, Y., Hirose, N., & Carninci, P.
- Affiliations
- RIKEN Center for Integrative Medical Sciences (JP)
- Keio University (JP)
- Corresponding author
- Hirose, Nobuyoshi
- Carninci, Piero
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-11-12
- Volume
- 116
- Issue
- 48
- Pages
- 24242-24251
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6883788
- OpenAlex
- W2983248500
- Cited by
- 343
- References
- 51
- Citations by year
- 2026: 45 · 2025: 49 · 2024: 56 · 2023: 59 · 2022: 51 · 2021: 52 · 2020: 28 · 2019: 3
- FWCI
- 13.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (17H04214, 19KK0222, 17H04090, 19H05747, 19H04820, 18K19569)
- RIKEN
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- supercentenarians, healthy aging, cytotoxic CD4+ T cells, clonal expansion, T cell receptor repertoire, peripheral blood mononuclear cells, immunosenescence, longevity, interferon-gamma, TNF-α
- MeSH terms
- Adult, Aged, Aged, 80 and over, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Humans, Interferon-gamma, Leukocytes, Mononuclear, Middle Aged, Tumor Necrosis Factor-alpha, CD4-Positive T-Lymphocytes, Case-Control Studies, Gene Expression Profiling, Single-Cell Analysis, Clonal Evolution
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