Epigenetics of T cell aging
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T cells are a heterogeneous population of cells that differ in their differentiation stages. Functional states are reflected in the epigenome that confers stability in cellular identity and is therefore important for naïve as well as memory T cell function. In many cellular systems, changes in chromatin structure due to alterations in histone expression, histone modifications and DNA methylation are characteristic of the aging process and cause or at least contribute to cellular dysfunction in senescence. Here, we review the epigenetic changes in T cells that occur with age and discuss them in the context of canonical epigenetic marks in aging model systems as well as recent findings of chromatin accessibility changes in T cell differentiation. Remarkably, transcription factor networks driving T cell differentiation account for many of the age-associated modifications in chromatin structures suggesting that loss of quiescence and activation of differentiation pathways are major components of T cell aging. Review on aging process in T cells is characterized by changes in chromatin structures, many of which resemble epigenetic modifications seen with differentiation.
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Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8+ T cells.
“Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8+ T cells144–147.”
From Measuring biological age using omics data (2022) · cites this paper as [147]
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López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Crystal structure of the nucleosome core particle at 2.8 Å resolution
Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F., & Richmond, T. J. (1997) · Nature · doi:10.1038/38444 · Cited by 9,466 · see citing works
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075 · see citing works
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013) · Nature Methods · doi:10.1038/nmeth.2688 · Cited by 6,422 · see citing works
Genome-wide methylation profiles reveal quantitative views of human aging rates
Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., Klotzle, B., Bibikova, M., Fan, J.-B., Gao, Y., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.016 · Cited by 4,270 · see citing works
The role of senescent cells in ageing
van Deursen, J. M. (2014) · Nature · doi:10.1038/nature13193 · Cited by 2,623 · see citing works
Single-cell chromatin accessibility reveals principles of regulatory variation
Buenrostro, J. D., Wu, B., Litzenburger, U. M., Ruff, D., Gonzales, M. L., Snyder, M. P., Chang, H. Y., & Greenleaf, W. J. (2015) · Nature · doi:10.1038/nature14590 · Cited by 2,308 · see citing works
Tan, M., Luo, H., Lee, S., Jin, F., Yang, J. S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.008 · Cited by 1,902 · see citing works
An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites
Skene, P. J., & Henikoff, S. (2017) · eLife · doi:10.7554/elife.21856 · Cited by 1,737 · see citing works
The DNA methyltransferase family: a versatile toolkit for epigenetic regulation
Lyko, F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.80 · Cited by 1,475 · see citing works
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D. R., Kurachi, M., et al. (2016) · Science · doi:10.1126/science.aaf2807 · Cited by 1,348 · see citing works
DNA methylation age of blood predicts all-cause mortality in later life
Marioni, R. E., Shah, S., McRae, A. F., Chen, B. H., Colicino, E., Harris, S. E., Gibson, J., Henders, A. K., Redmond, P., Cox, S. R., et al. (2015) · Genome Biology · doi:10.1186/s13059-015-0584-6 · Cited by 1,261 · see citing works
The twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240 · see citing works
Role of TET enzymes in DNA methylation, development, and cancer
Rasmussen, K. D., & Helin, K. (2016) · Genes & Development · doi:10.1101/gad.276568.115 · Cited by 1,040 · see citing works
Bocklandt, S., Lin, W., Sehl, M. E., Sánchez, F. J., Sinsheimer, J. S., Horvath, S., & Vilain, E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014821 · Cited by 1,012 · see citing works
The epigenetic landscape of T cell exhaustion
Sen, D. R., Kaminski, J., Barnitz, R. A., Kurachi, M., Gerdemann, U., Yates, K. B., Tsao, H.-W., Godec, J., LaFleur, M. W., Brown, F. D., et al. (2016) · Science · doi:10.1126/science.aae0491 · Cited by 986 · see citing works
Epigenetic mechanisms of longevity and aging
Sen, P., Shah, P. P., Nativio, R., & Berger, S. L. (2016) · Cell · doi:10.1016/j.cell.2016.07.050 · Cited by 956 · see citing works
Pal, S., & Tyler, J. K. (2016) · Science Advances · doi:10.1126/sciadv.1600584 · Cited by 860 · see citing works
Distinct DNA methylomes of newborns and centenarians
Heyn, H., Li, N., Ferreira, H. J., Moran, S., Pisano, D. G., Gomez, A., Diez, J., Sanchez-Mut, J. V., Setien, F., Carmona, F. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120658109 · Cited by 802 · see citing works
Diversity and clonal selection in the human T-cell repertoire
Qi, Q., Liu, Y., Cheng, Y., Glanville, J., Zhang, D., Lee, J.-Y., Olshen, R. A., Weyand, C. M., Boyd, S. D., & Goronzy, J. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409155111 · Cited by 755 · see citing works
Self-citationGleyzer, N., Vercauteren, K., & Scarpulla, R. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.4.1354-1366.2005 · Cited by 711 · see citing works
Sun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.03.002 · Cited by 686 · see citing works
Histone H4 lysine 16 acetylation regulates cellular lifespan
Dang, W., Steffen, K. K., Perry, R., Dorsey, J. A., Johnson, F. B., Shilatifard, A., Kaeberlein, M., Kennedy, B. K., & Berger, S. L. (2009) · Nature · doi:10.1038/nature08085 · Cited by 667 · see citing works
Expression switching in the stevor and Pfmc‐2TM superfamilies in Plasmodium falciparum
Lavazec, C., Sanyal, S., & Templeton, T. J. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.05767.x · Cited by 659 · see citing works
Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans
den Braber, I., Mugwagwa, T., Vrisekoop, N., Westera, L., Mögling, R., Bregje de Boer, A., Willems, N., Schrijver, E. H. R., Spierenburg, G., Gaiser, K., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.02.006 · Cited by 572 · see citing works
Lipin 1 is an inducible amplifier of the hepatic PGC-1α/PPARα regulatory pathway
Finck, B. N., Gropler, M. C., Chen, Z., Leone, T. C., Croce, M. A., Harris, T. E., Lawrence, J. C., & Kelly, D. P. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.08.005 · Cited by 555 · see citing works
Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging
Liu, L., Cheung, T. H., Charville, G. W., Hurgo, B. M. C., Leavitt, T., Shih, J., Brunet, A., & Rando, T. A. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.043 · Cited by 544 · see citing works
Kerdiles, Y. M., Beisner, D. R., Tinoco, R., Dejean, A. S., Castrillón, D. H., DePinho, R. A., & Hedrick, S. Μ. (2009) · Nature Immunology · doi:10.1038/ni.1689 · Cited by 541 · see citing works
Origin and differentiation of human memory CD8 T cells after vaccination
Akondy, R. S., Fitch, M., Edupuganti, S., Yang, S., Kissick, H. T., Li, K. W., Youngblood, B. A., Abdelsamed, H. A., McGuire, D. J., Cohen, K. W., et al. (2017) · Nature · doi:10.1038/nature24633 · Cited by 517 · see citing works
Self-citationCompetition between DNA methylation and transcription factors determines binding of NRF1
Domcke, S., Bardet, A. F., Adrian Ginno, P., Hartl, D., Burger, L., & Schübeler, D. (2015) · Nature · doi:10.1038/nature16462 · Cited by 508 · see citing works
Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease
DuPage, M. J. P., & Bluestone, J. A. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2015.18 · Cited by 507 · see citing works
Epigenetic control of CD8+ T cell differentiation
Henning, A. N., Roychoudhuri, R., & Restifo, N. P. (2018) · Nature reviews. Immunology · doi:10.1038/nri.2017.146 · Cited by 501 · see citing works
T cell subset-specific susceptibility to aging
Czesnikiewicz-Guzik, M., Lee, W.-W., Cui, D., Hiruma, Y., Lamar, D. L., Yang, Z.-Z., Ouslander, J. G., Weyand, C. M., & Goronzy, J. J. (2008) · Clinical Immunology · doi:10.1016/j.clim.2007.12.002 · Cited by 478 · see citing works
Self-citationElevated histone expression promotes life span extension
Feser, J., Truong, D., Das, C., Carson, J. J., Kieft, J., Harkness, T., & Tyler, J. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.08.015 · Cited by 435 · see citing works
Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres
O'Sullivan, R. J., Kubicek, S., Schreiber, S. L., & Karlseder, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1897 · Cited by 416 · see citing works
Using DNA methylation profiling to evaluate biological age and longevity interventions
Petkovich, D. A., Podolskiy, D. I., Lobanov, A. V., Lee, S.-G., Miller, R. A., & Gladyshev, V. N. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.016 · Cited by 398 · see citing works
Scarpulla, R. C. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.006 · Cited by 389 · see citing works
Schep, A. N., Buenrostro, J. D., Denny, S. K., Schwartz, K., Sherlock, G., & Greenleaf, W. J. (2015) · Genome Research · doi:10.1101/gr.192294.115 · Cited by 375 · see citing works
Day, K. R., Waite, L. L., Thalacker‐Mercer, A. E., West, A. B., Bamman, M. M., Brooks, J. D., Myers, R., & Absher, D. (2013) · Genome biology · doi:10.1186/gb-2013-14-9-r102 · Cited by 363 · see citing works
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362 · see citing works
Self-citationWertheimer, A. M., Bennett, M. S., Park, B., Uhrlaub, J. L., Martinez, C., Pulko, V., Currier, N. L., Nikolich-Žugich, D., Kaye, J., & Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301721 · Cited by 352 · see citing works
Hu, Z., Chen, K., Xia, Z., Chavez-Tomar, M., Pal, S., Seol, J.-H., Chen, C., Li, W., & Tyler, J. K. (2014) · Genes & Development · doi:10.1101/gad.233221.113 · Cited by 330 · see citing works
BACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancers
Roychoudhuri, R., Clever, D. C., Li, P., Wakabayashi, Y., Quinn, K. M., Klebanoff, C. A., Ji, Y., Sukumar, M., Eil, R. L., Yu, Z., et al. (2016) · Nature Immunology · doi:10.1038/ni.3441 · Cited by 317 · see citing works
Dynamic Changes in Chromatin Accessibility Occur in CD8 + T Cells Responding to Viral Infection
Scott-Browne, J. P., López-Moyado, I. F., Trifari, S., Wong, V., Chávez, L., Rao, A., & Pereira, R. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.028 · Cited by 309 · see citing works
Chandra, T., Kirschner, K., Thuret, J.-Y., Pope, B. D., Ryba, T., Newman, S., Ahmed, K., Samarajiwa, S. A., Salama, R., Carroll, T., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.010 · Cited by 308 · see citing works
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
Weng, N.-P., Araki, Y., & Subedi, K. (2012) · Nature Reviews Immunology · doi:10.1038/nri3173 · Cited by 290 · see citing works
Reconfiguration of DNA methylation in aging
Zampieri, M., Ciccarone, F., Calabrese, R., Franceschi, C., Bürkle, A., & Caiafa, P. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.02.002 · Cited by 254 · see citing works
Epigenomics of human CD8 T cell differentiation and aging
Moskowitz, D. M., Zhang, D. W., Hu, B., Le Saux, S., Yanes, R. E., Ye, Z., Buenrostro, J. D., Weyand, C. M., Greenleaf, W. J., & Goronzy, J. J. (2017) · Science Immunology · doi:10.1126/sciimmunol.aag0192 · Cited by 252 · see citing works
Self-citationHomeostatic proliferation and survival of naïve and memory T cells
Boyman, O., Létourneau, S., Krieg, C., & Sprent, J. (2009) · European Journal of Immunology · doi:10.1002/eji.200939444 · Cited by 251 · see citing works
Gray, S. M., Amezquita, R. A., Guan, T., Kleinstein, S. H., & Kaech, S. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.012 · Cited by 245 · see citing works
Mechanisms for the Inheritance of Chromatin States
Moazed, D. (2011) · Cell · doi:10.1016/j.cell.2011.07.013 · Cited by 243 · see citing works
The epigenetic control of stemness in CD8 + T cell fate commitment
Pace, L., Goudot, C., Zueva, E., Gueguen, P., Burgdorf, N., Waterfall, J. J., Quivy, J., Almouzni, G., & Amigorena, S. (2018) · Science · doi:10.1126/science.aah6499 · Cited by 232 · see citing works
Differentiation of CD8 memory T cells depends on Foxo1
Michelini, R. H., Doedens, A. L., Goldrath, A. W., & Hedrick, S. Μ. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20130392 · Cited by 228 · see citing works
Tcf1 and Lef1 transcription factors establish CD8+ T cell identity through intrinsic HDAC activity
Xing, S., Li, F., Zeng, Z., Zhao, Y., Yu, S., Shan, Q., Li, Y., Phillips, F. C., Maina, P. K., Qi, H. H., et al. (2016) · Nature Immunology · doi:10.1038/ni.3456 · Cited by 226 · see citing works
Fuertes Marraco, S. A., Soneson, C., Cagnon, L., Gannon, P. O., Allard, M., Maillard, S. A., Montandon, N., Rufer, N., Waldvogel, S., Delorenzi, M., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa3700 · Cited by 206 · see citing works
Reynolds, L. M., Taylor, J. R., Ding, J., Lohman, K., Johnson, C. W., Siscovick, D. S., Burke, G. L., Post, W. S., Shea, S., Jacobs, D. R., et al. (2014) · Nature Communications · doi:10.1038/ncomms6366 · Cited by 201 · see citing works
The chromatin accessibility signature of human immune aging stems from CD8+ T cells
Ucar, D., Márquez, E. J., Chung, C.-H., Marches, R., Rossi, R. J., Uyar, A., Wu, T.-C., George, J., Stitzel, M. L., Palucka, A. K., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170416 · Cited by 200 · see citing works
Celona, B., Weiner, A., Felice, F. D., Mancuso, F. M., Cesarini, E., Rossi, R. L., Gregory, L., Baban, D. F., Rossetti, G., Grianti, P., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001086 · Cited by 198 · see citing works
Tserel, L., Kolde, R., Limbach, M., Tretyakov, K., Kasela, S., Kisand, K. E., Saare, M., Vilo, J., Metspalu, A., Milani, L. A., et al. (2015) · Scientific Reports · doi:10.1038/srep13107 · Cited by 182 · see citing works
Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses
Pulko, V., Davies, J. S., Martinez, C., Lanteri, M. C., Busch, M. P., Diamond, M. S., Knox, K., Bush, E. C., Sims, P. A., Sinari, S., et al. (2016) · Nature Immunology · doi:10.1038/ni.3483 · Cited by 175 · see citing works
Redefining CpG islands using hidden Markov models
Wu, H., Caffo, B. S., Jaffee, H. A., Irizarry, R. A., & Feinberg, A. P. (2010) · Biostatistics · doi:10.1093/biostatistics/kxq005 · Cited by 166 · see citing works
Rai, T. S., Cole, J. J., Nelson, D. M., Dikovskaya, D., Faller, W. J., Vizioli, M. G., Hewitt, R. N., Anannya, O., McBryan, T., Manoharan, I., et al. (2014) · Genes & Development · doi:10.1101/gad.247528.114 · Cited by 162 · see citing works
Ladle, B. H., Li, K.-P., Phillips, M. J., Pucsek, A. B., Haile, A., Powell, J. D., Jaffee, E. M., Hildeman, D. A., & Gamper, C. J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524490113 · Cited by 152 · see citing works
Individuality and Variation of Personal Regulomes in Primary Human T Cells
Qu, K., Zaba, L. C., Giresi, P. G., Li, R., Longmire, M. R., Kim, Y. H., Greenleaf, W. J., & Chang, H. Y. (2015) · Cell Systems · doi:10.1016/j.cels.2015.06.003 · Cited by 151 · see citing works
Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
Abdelsamed, H. A., Moustaki, A., Fan, Y., Dogra, P., Ghoneim, H. E., Zebley, C. C., Triplett, B. M., Sékaly, R., & Youngblood, B. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161760 · Cited by 147 · see citing works
Rendeiro, A. F., Schmidl, C., Strefford, J. C., Walewska, R., Davis, Z., Farlik, M., Oscier, D., & Bock, C. (2016) · Nature Communications · doi:10.1038/ncomms11938 · Cited by 146 · see citing works
Convergence of Innate and Adaptive Immunity during Human Aging
Pereira, B. I., & Akbar, A. N. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00445 · Cited by 106 · see citing works
Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging
Whiting, C. C., Siebert, J., Newman, A. M., Du, H.-W., Alizadeh, A. A., Goronzy, J. J., Weyand, C. M., Krishnan, E., Fathman, C. G., & Maecker, H. T. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133627 · Cited by 100 · see citing works
Self-citationHeterochromatin and its Relationship to Cell Senescence and Cancer Therapy
Zhang, R.-G., & Adams, P. (2007) · Cell Cycle · doi:10.4161/cc.6.7.4079 · Cited by 99 · see citing works
Abnormal Epigenetic Regulation of Immune System during Aging
Jasiulionis, M. G. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00197 · Cited by 99 · see citing works
Delpoux, A., Lai, C.-Y., Hedrick, S. Μ., & Doedens, A. L. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618916114 · Cited by 91 · see citing works
Acevedo, N., Reinius, L. E., Vitezic, M., Fortino, V., Söderhäll, C., Honkanen, H., Veijola, R., Simell, O., Toppari, J., Ilonen, J., et al. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0064-6 · Cited by 88 · see citing works
Ciccarone, F., Malavolta, M., Calabrese, R., Guastafierro, T., Bacalini, M. G., Reale, A., Franceschi, C., Capri, M., Hervonen, A., Hurme, M., et al. (2016) · Aging Cell · doi:10.1111/acel.12485 · Cited by 77 · see citing works
Liu, Y., Chen, Y., & Richardson, B. (2009) · Clinical Immunology · doi:10.1016/j.clim.2009.03.529 · Cited by 73 · see citing works
The chromatin landscape and transcription factors in T cell programming
Rothenberg, E. V. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.03.001 · Cited by 70 · see citing works
Rodríguez, R. M. A., Suárez-Álvarez, B., Lavín, J. L., Mosén-Ansorena, D., Raneros, A. B., Márquez‐Kisinousky, L., Aransay, A. M., & López‐Larrea, C. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1601102 · Cited by 65 · see citing works
Transcriptional instability is not a universal attribute of aging
Warren, L. A., Rossi, D. J., Schiebinger, G. R., Weissman, I. L., Kim, S. K., & Quake, S. R. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00337.x · Cited by 56 · see citing works
Suárez-Álvarez, B., Rodríguez, R. M. A., Schlangen, K., Raneros, A. B., Márquez‐Kisinousky, L., Fernández, A. F., Díaz‐Corte, C., Aransay, A. M., & López‐Larrea, C. (2016) · Aging Cell · doi:10.1111/acel.12552 · Cited by 48 · see citing works
Functional pathways regulated by microRNA networks in CD8 T‐cell aging
Gustafson, C. E., Cavanagh, M., Jin, J., Weyand, C. M., & Goronzy, J. J. (2018) · Aging Cell · doi:10.1111/acel.12879 · Cited by 45 · see citing works
Self-citationBrettingham‐Moore, K. H., Taberlay, P. C., & Holloway, A. F. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00499 · Cited by 34 · see citing works
CpG Islands in Cancer: Heads, Tails, and Sides
Ferreira, H. J., & Esteller, M. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7768-0_4 · Cited by 30 · see citing works
Silencing stemness in T cell differentiation
Henning, A. N., Klebanoff, C. A., & Restifo, N. P. (2018) · Science · doi:10.1126/science.aar5541 · Cited by 20 · see citing works
Ucar, D., & Benayoun, B. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-811060-7.00001-2 · Cited by 12 · see citing works
Warrington (2001) · Pure Amsterdam UMC · doi:10.1002/1529-0131(200101)44:1 · Cited by 2 · see citing works
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Measuring biological age using omics data
Rutledge, J., Oh, H., & Wyss-Coray, T. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00511-7 · Cited by 570 · see citing works
“Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8 + T cells 144–147 .”
BackgroundMechanisms underlying T cell ageing
Goronzy, J. J., & Weyand, C. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0180-1 · Cited by 506 · see citing works
Self-citationWiertsema, S. P., van Bergenhenegouwen, J., Garssen, J., & Knippels, L. M. J. (2021) · Nutrients · doi:10.3390/nu13030886 · Cited by 558 · see citing works
“In addition, intricate alterations occur in T cells with increasing age, including epigenetic and metabolic changes, which affect naïve-, memory-, and effector T cells [86,87].”
BackgroundInfluence of immune aging on vaccine responses
Gustafson, C. E., Kim, C., Weyand, C. M., & Goronzy, J. J. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.017 · Cited by 286 · see citing works
“Loss of polyfunctionality may be a consequence of more progressed or end-differentiation, as indicated by the chromatin state of old central memory T cells or the increased frequencies of terminally differentiated effector memory cells (TEMRAs).(130) An alternative explanation is that memory T cells in older individua…”
Self-citationOh, S. J., Lee, J. K., & Shin, O. S. (2019) · Immune Network · doi:10.4110/in.2019.19.e37 · Cited by 261 · see citing works
“T cells T cells undergo profound and complex changes with aging, including epigenetic and metabolic modifications, affecting a range of subsets including naïve, memory, and effector T cells (61,62).”
BackgroundVella, L. A., Giles, J. R., Baxter, A. E., Oldridge, D. A., Diorio, C. J., Kuri-Cervantes, L., Alanio, C., Pampena, M. B., Wu, J. E., Chen, Z., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abf7570 · Cited by 219 · see citing works
“As expected (36), the frequency of naive CD4+ and CD8+”
Metabolic programs tailor T cell immunity in viral infection, cancer, and aging
Møller, S. H., Hsueh, P., Yu, Y.-R., Zhang, L., & Ho, P. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.02.003 · Cited by 148 · see citing works
Pathogenesis of Giant Cell Arteritis and Takayasu Arteritis—Similarities and Differences
Watanabe, R., Berry, G. J., Liang, D. H., Goronzy, J. J., & Weyand, C. M. (2020) · Current Rheumatology Reports · doi:10.1007/s11926-020-00948-x · Cited by 129 · see citing works
Self-citationSalminen, A. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02123-w · Cited by 124 · see citing works
“The epigenetic hallmarks of T cell aging include a global decrease in DNA methylation, whereas there is an increase in the number of heterogeneous loci of methylated CpG [175].”
BackgroundKarakaslar, E. O., Katiyar, N., Hasham, M., Youn, A., Sharma, S., Chung, C., Marches, R., Korstanje, R., Banchereau, J., & Ucar, D. (2023) · Aging Cell · doi:10.1111/acel.13792 · Cited by 98 · see citing works
Vaccination as a preventative measure contributing to immune fitness
Laupèze, B., Giudice, G. D., Doherty, M. T., & der Most, R. G. V. (2021) · npj Vaccines · doi:10.1038/s41541-021-00354-z · Cited by 97 · see citing works
The Transcription Factor TCF1 in T Cell Differentiation and Aging
Kim, C., Jin, J., Weyand, C. M., & Goronzy, J. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186497 · Cited by 81 · see citing works
Self-citationMonocytes present age-related changes in phospholipid concentration and decreased energy metabolism
Saare, M., Tserel, L., Haljasmägi, L., Taalberg, E., Peet, N., Eimre, M., Vetik, R., Kingo, K., Saks, K., Tamm, R., et al. (2020) · Aging Cell · doi:10.1111/acel.13127 · Cited by 79 · see citing works
Immune Aging and Immunotherapy in Cancer
Kaiser, M., Semeraro, M. D., Herrmann, M., Absenger, G., Gerger, A., & Renner, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22137016 · Cited by 78 · see citing works
Márquez, E. J., Trowbridge, J. J., Kuchel, G. A., Banchereau, J., & Ucar, D. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00183-z · Cited by 71 · see citing works
Clinical perspectives on the age-related increase of immunosuppressive activity
Salminen, A. (2022) · Journal of Molecular Medicine · doi:10.1007/s00109-022-02193-4 · Cited by 57 · see citing works
Transcription factor networks in aged naïve CD4 T cells bias lineage differentiation
Hu, B., Li, G., Ye, Z., Gustafson, C. E., Tian, L., Weyand, C. M., & Goronzy, J. J. (2019) · Aging Cell · doi:10.1111/acel.12957 · Cited by 60 · see citing works
“Our data on TF networks in naïve CD4 T cells are consistent with the concept that immune aging involves the activation of T‐cell differ‐ entiation pathways resulting in a loss of naivety and stemness (Goronzy et al., 2018).”
BackgroundSelf-citationThe metabolic signature of T cells in rheumatoid arthritis
Weyand, C. M., Wu, B., & Goronzy, J. J. (2019) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000683 · Cited by 59 · see citing works
“T cell aging is also coupled to a fundamental change in cellular metabolism [20,21].”
BackgroundSelf-citationFOXO1 deficiency impairs proteostasis in aged T cells
Jin, J., Li, X., Hu, B., Kim, C., Cao, W., Zhang, H., Weyand, C. M., & Goronzy, J. J. (2020) · Science Advances · doi:10.1126/sciadv.aba1808 · Cited by 54 · see citing works
Self-citationmiR-181a-regulated pathways in T-cell differentiation and aging
Kim, C., Ye, Z., Weyand, C. M., & Goronzy, J. J. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00240-1 · Cited by 54 · see citing works
“In general, histone loss is one of the hallmarks of aging in several model systems [64, 65],”
BackgroundSelf-citationSenescence in Pulmonary Fibrosis: Between Aging and Exposure
Venosa, A. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.606462 · Cited by 48 · see citing works
“Epigenetic analysis of aged senescent lymphocytes demonstrate progressive expansion of reactive effector cells (i.e., Th17) through DNA hypermethylation of transcriptional regulators essential to T cell responses (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27, and CD248) and differentiation (SATB1, TCF7, BCL11B, and RUNX3) (31…”
BackgroundInfluentialMetabolic reprogramming in memory CD4 T cell responses of old adults
Yanes, R. E., Zhang, H., Shen, Y., Weyand, C. M., & Goronzy, J. J. (2019) · Clinical Immunology · doi:10.1016/j.clim.2019.07.003 · Cited by 47 · see citing works
Self-citationHistone deficiency and accelerated replication stress in T cell aging
Kim, C., Jin, J., Ye, Z., Jadhav, R. R., Gustafson, C. E., Hu, B., Cao, W., Tian, L., Weyand, C. M., & Goronzy, J. J. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143632 · Cited by 47 · see citing works
Self-citationT cell aging as a risk factor for autoimmunity
Liu, Q., Zheng, Y., Goronzy, J. J., & Weyand, C. M. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102947 · Cited by 45 · see citing works
Self-citationKarpuzoglu, E., Holladay, S. D., & Gogal, R. M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1704203 · Cited by 43 · see citing works
Age as a risk factor in vasculitis
Gloor, A. D., Berry, G. J., Goronzy, J. J., & Weyand, C. M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00911-1 · Cited by 43 · see citing works
“5) [83].”
Self-citationRole of T Cells in the Pathogenesis of Rheumatoid Arthritis: Focus on Immunometabolism Dysfunctions
Masoumi, M., Alesaeidi, ., Khorramdelazad, H., Behzadi, M., Baharlou, R., Alizadeh‐Fanalou, S., & Karami, J. (2022) · Inflammation · doi:10.1007/s10753-022-01751-9 · Cited by 38 · see citing works
“Furthermore, T cell aging is associated with massive alterations in the cellular metabolic pathways [101, 102].”
BackgroundT cell aging and Alzheimer’s disease
Guo, L., Li, X., Gould, T. M., Wang, Z., & Cao, W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1154699 · Cited by 33 · see citing works
Conserved epigenetic hallmarks of T cell aging during immunity and malignancy
Tian, M., Soerens, A. G., Alli, S., Kang, T. G., Vasandan, A. B., Wang, Z., Vezys, V., Kimura, S., Iacobucci, I., Baylin, S. B., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00649-5 · Cited by 30 · see citing works
“The relationship between human chronologic age and T cell epigenetics has been previously described by several groups 42 , documenting an enrichment of memory-associated epigenetic programs in aged populations.”
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 20 · see citing works
“This shift reflects a broader decline in the immune responses, with aged T cells demonstrating altered metabolic profiles [48, 49, 56].”
Gut Feelings: How Microbes, Diet, and Host Immunity Shape Disease
Theis, B. F., Park, J. S., Kim, J. S., Zeydabadinejad, S., Vijay–Kumar, M., Yeoh, B. S., & Saha, P. (2025) · Biomedicines · doi:10.3390/biomedicines13061357 · Cited by 24 · see citing works
Conway, J., Certo, M., Lord, J. M., Mauro, C., & Duggal, N. A. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15671 · Cited by 19 · see citing works
“…al., 2013), which include accumulation of DNA damage, telomere shortening (Akbar & Fletcher, 2005), reduced mitochondrial function (Callender et al., 2020), reduced autophagy (Alsaleh et al., 2020), chronic inflammation (Jose et al., 2017) and epigenetic changes (Goronzy et al., 2018) (Figure 1).”
BackgroundImmune Cells and Immunosenescence
Bischof, J., Gärtner, F., Zeiser, K., Kunz, R., Schreiner, C., Hoffer, E., Burster, T., Knippschild, U., & Zimecki, M. (2019) · Folia Biologica · doi:10.14712/fb2019065020053 · Cited by 18 · see citing works
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 17 · see citing works
“Recent research reports have highlighted significant changes in chromatin modifications of human immune cell epigenetic phenotypes (Goronzy et al., 2018).”
Decoding T cell senescence in cancer: Is revisiting required?
Magkouta, S., Markaki, E., Evangelou, K., Petty, R., Verginis, P., & Gorgoulis, V. G. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.11.003 · Cited by 17 · see citing works
Lymphoma accelerates T cell and tissue aging
Hesterberg, R. S., Davis, J. T., Handoo, K. J., Elmarsafawi, A. G., Augello, A. C., Cheng, C., Atkins, R. M., Lee, D. H., Yang, C., Yao, J., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.07.023 · Cited by 14 · see citing works
Lu, S., Yadav, A. K., & Qiao, X. (2020) · Hematology · doi:10.1080/16078454.2020.1757332 · Cited by 13 · see citing works
Stanel, S. C., Callum, J., & Rivera‐Ortega, P. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1232655 · Cited by 13 · see citing works
“Cellular senescence is characterized by a state of cell cycle arrest (31).”
BackgroundT cell aging and exhaustion: Mechanisms and clinical implications
Zhang, W., Kong, D., Zhang, X., Hu, L., Nian, Y., & Shen, Z. (2025) · Clinical Immunology · doi:10.1016/j.clim.2025.110486 · Cited by 11 · see citing works
Shen, M., Tang, W., Cheng, Z., Qi, Z., Chen, Z., Tian, Y., Zhang, Y., He, Q., Shi, H., Zhu, H., et al. (2020) · The Journal of Comparative Neurology · doi:10.1002/cne.25018 · Cited by 11 · see citing works
Judge, S. J., Bloomstein, J. D., Sholevar, C. J., Darrow, M. A., Stoffel, K. M., Vick, L. V., Dunai, C., Cruz, S. M., Razmara, A. M., Monjazeb, A. M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.893177 · Cited by 10 · see citing works
“Transcriptomic Analysis of Peripheral and Tumor-Infiltrating Immune Cells Highlights Distinct Changes in Gene Expression Patterns Between NK and T Cells in Soft Tissue Sarcomas There is currently a thorough and evolving understanding of the genetic and epigenetic changes in tumor-infiltrating T cells which distinguish…”
BackgroundLagousi, T., Basdeki, P., de Jonge, M. I., & Spoulou, V. I. (2020) · Expert Review of Vaccines · doi:10.1080/14760584.2020.1843433 · Cited by 9 · see citing works
Transcriptome-based measurement of CD8+ T cell age and its applications
Weng, N. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.05.005 · Cited by 8 · see citing works
Regulatory RNAs in immunosenescence
Talepoor, A. G., & Doroudchi, M. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1209 · Cited by 7 · see citing works
Metabolic Signaling as a Driver of T Cell Aging
Choi, M. S., Choi, S., Cho, M., & Kim, C. (2025) · Immune Network · doi:10.4110/in.2025.25.e14 · Cited by 8 · see citing works
“Aging induces significant changes in the epigenetic landscape that regulates transcriptional programs (40).”
Self-citationGillespie, S. L., Hardy, L. R., & Anderson, C. M. (2019) · Nursing Outlook · doi:10.1016/j.outlook.2019.05.006 · Cited by 7 · see citing works
Possibilities of using T-cell biophysical biomarkers of ageing
González‐Bermúdez, B., Abarca‐Ortega, A., González-Sánchez, M., la Fuente, M. D., & Plaza, G. R. (2022) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.29 · Cited by 5 · see citing works
Gut-Immune Interplay: Decoding the Microbiome’s Impact on Immunity and Diseases
Khazi, A. I., & Ahmad, A. (2025) · Journal of Pharmacy And Bioallied Sciences · doi:10.4103/jpbs.jpbs_1377_25 · Cited by 4 · see citing works
Maintaining a ‘fit’ immune system: the role of vaccines
Laupèze, B., & Doherty, T. M. (2023) · Expert Review of Vaccines · doi:10.1080/14760584.2023.2185223 · Cited by 5 · see citing works
“In effect, these changes alter the levels of gene transcription and can lead to immune system dysregulation [52,55].”
BackgroundHan, J., Ma, Y., Lv, W., Wang, J., Wu, Y. H., Niu, H., Mi, Y., Li, F., & Zhu, B. (2022) · Molecular Immunology · doi:10.1016/j.molimm.2022.04.013 · Cited by 4 · see citing works
Imran, S., Neeland, M. R., Martino, D., Peng, S., Koplin, J. J., Dharmage, S. C., Tang, M. L. K., Sawyer, S. M., Dang, T. D., McWilliam, V. L., et al. (2023) · Immunology and Cell Biology · doi:10.1111/imcb.12628 · Cited by 2 · see citing works
“To date, studies examining epigenetic processes associated with T cell development have largely focused on chromatin and histone modifications.(11,14) DNAm studies assessing changes associated with T cell activation have mainly used targeted approaches focused on selected genes and gene promoter and thus there is limi…”
BackgroundThe genetic regulation of immune cells upon activation
Sánchez-Tarjuelo, R. (2025) · Advances in genetics · doi:10.1016/bs.adgen.2025.11.009 · Cited by 1 · see citing works
Handono, K., Pratama, M. Z., Yuniati, M. G., Sermoati, I. A., Norahmawati, E., Endharti, A. T., Irwanto, Y., Hidayat, S., Solikhin, M. B., Indahwati, L., et al. (2023) · AIP conference proceedings · doi:10.1063/5.0117337 · Cited by 1 · see citing works
Karakaslar, E. O., Hasham, M. G., Katiyar, N., Youn, A., Sharma, S. M., Chung, C., Marcheş, R., Korstanje, R., Banchereau, J., & Ucar, D. (2021) · Research Square · doi:10.21203/rs.3.rs-1051151/v1
Faculty Opinions recommendation of FOXO1 deficiency impairs proteostasis in aged T cells.
Chakraborty, K. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737807256.793587855
Fu, M. P., Edwards, K., Navarro‐Delgado, E. I., Merrill, S. M., Kitaba, N. T., Konwar, C., Mandhane, P. J., Simons, E., Subbarao, P., Moraes, T. J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.22.649907
“To address this methodological gap, it is crucial to note that not only does the cellular composition of blood varies with age, but so does the DNAme profile of sorted cells 37,45– 47 .”
Zhang, C., & Zhang, J. (2026) · Biogerontology · doi:10.1007/s10522-026-10453-w
“As age advances, naive T cell output declines, memory and effector T cells accumulate, and CD8 + T cells progressively acquire an exhausted phenotype, resulting in impaired responsiveness to novel antigens (Goronzy et al. 2018).”
Wu, D., Zhang, P., & Zeng, C. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.101536
- Authors
- Goronzy, J. J., Hu, B., Kim, C., Jadhav, R. R., & Weyand, C. M.
- Affiliations
- VA Palo Alto Health Care System (US)
- Corresponding author
- Goronzy, Jörg J
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-06-27
- Volume
- 104
- Issue
- 4
- Pages
- 691-699
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC6162101
- OpenAlex
- W2810131496
- Cited by
- 60
- References
- 86
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 7
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AR042527, R01 HL117913, R01 AI108906, P01 HL129941, R01 AI108891, R01 AG045779, U19 AI057266, R01 AI129191, I01 BX001669, R01 AI108906,)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- T cell senescence, epigenetics, chromatin accessibility, histone modifications, DNA methylation, cellular senescence, T cell differentiation, transcriptional regulatory networks, memory T cells, naive T cells
- MeSH terms
- Aging, Animals, Chromatin, Gene Expression Regulation, Histones, Humans, Mammals, T-Lymphocytes, Transcription Factors, Cellular Senescence, Lymphopoiesis, Epigenesis, Genetic, Transcriptome
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