Telomerase insufficiency in rheumatoid arthritis
Open accessAbstract
In rheumatoid arthritis (RA), chronically stimulated T lymphocytes sustain tissue-destructive joint inflammation. Both naïve and memory T cells in RA are prematurely aged with accelerated loss of telomeres suggesting excessive proliferative pressure or inadequate telomeric maintenance. Upon stimulation, RA naïve CD4 T cells are defective in up-regulating telomerase activity ( P < 0.0001) due to insufficient induction of the telomerase component human telomerase reverse transcriptase (hTERT); T cell activation and cell cycle progression are intact. Telomerase insufficiency does not affect memory T cells or CD34 hematopoietic stem cells and is present in untreated patients and independent from disease activity. Knockdown of hTERT in primary human T cells increases apoptotic propensity ( P = 0.00005) and limits clonal burst ( P = 0.0001) revealing a direct involvement of telomerase in T cell fate decisions. Naïve RA CD4 T cells stimulated through the T cell receptor are highly susceptible to apoptosis, expanding to smaller clonal size. Overexpression of ectopic hTERT in naïve RA T cells conveys apoptotic resistance ( P = 0.008) and restores proliferative expansion ( P < 0.0001). Telomerase insufficiency in RA results in excessive T cell loss, undermining homeostatic control of the naive T cell compartment and setting the stage for lymphopenia-induced T cell repertoire remodeling. Restoring defective telomerase activity emerges as a therapeutic target in resetting immune abnormalities in RA.
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Early studies using telomeric length and clonal expansion of CD4+CD28− end-differentiated T cells estimated that immune aging is accelerated by 2-3 decades in RA patients compared to age-matched controls.
“Early studies, utilizing measurements of telomeric length and clonal expansion of CD4+CD28− end-differentiated T cells, estimated that the immune aging process is accelerated by 2–3 decades in patients with RA as compared to age-matched controls”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Fujii et al., 2009
Telomerase upregulation is defective in RA patients, which shortens T cell longevity.
“This mechanism of telomerase upregulation is defective in patients with RA, shortening the longevity of T cells [14].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [14]
The telomerase upregulation that compensates for telomere erosion is defective in T cells from rheumatoid arthritis patients.
“This compensatory mechanism is defective in RA T cells [14,53].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [14]
Naive T cells undergo 30 to 40 population doublings during priming alone.
“It is also estimated that naïve T cells expand by 30–40 population doublings during priming alone [14].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [14]
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Cites
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438 · see citing works
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
Telomere measurement by quantitative PCR
Cawthon, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e47 · Cited by 3,492 · see citing works
Shelterin: the protein complex that shapes and safeguards human telomeres
de Lange, T. (2005) · Genes & Development · doi:10.1101/gad.1346005 · Cited by 3,056 · see citing works
Switching and Signaling at the Telomere
Blackburn, E. H. (2001) · Cell · doi:10.1016/s0092-8674(01)00492-5 · Cited by 2,097 · see citing works
Doran, M. F., Crowson, C. S., Pond, G. R., O’Fallon, W. M., & Gabriel, S. E. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10524 · Cited by 1,213 · see citing works
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · see citing works
The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita
Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P. J., & Dokal, I. (2001) · Nature · doi:10.1038/35096585 · Cited by 960 · see citing works
McEachern, M. J., Krauskopf, A., & Blackburn, E. H. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.331 · Cited by 716 · see citing works
Quah, B., Warren, H. S., & Parish, C. R. (2007) · Nature Protocols · doi:10.1038/nprot.2007.296 · Cited by 628 · see citing works
T cell homeostasis in patients with rheumatoid arthritis
Koetz, K., Bryl, E., Spickschen, K., O’Fallon, W. M., Goronzy, J. J., & Weyand, C. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.9203 · Cited by 467 · see citing works
Self-citationArmanios, M., Chen, J.-L., Chang, Y.-P. C., Brodsky, R. A., Hawkins, A., Griffin, C. A., Eshleman, J. R., Cohen, A. R., Chakravarti, A., Hamosh, A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508124102 · Cited by 452 · see citing works
Regulated expression of telomerase activity in human T lymphocyte development and activation.
Weng, N., Levine, B. L., June, C. H., & Hodes, R. J. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2471 · Cited by 403 · see citing works
Telomeres: Cancer to Human Aging
Stewart, S. A., & Weinberg, R. A. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104518 · Cited by 336 · see citing works
Hodes, R. J., Hathcock, K. S., & Weng, N. (2002) · Nature reviews. Immunology · doi:10.1038/nri890 · Cited by 315 · see citing works
Mechanism of Telomerase Induction during T Cell Activation
Bodnar, A. G., Kim, N. W., Effros, R. B., & Chiu, C. (1996) · Experimental Cell Research · doi:10.1006/excr.1996.0299 · Cited by 285 · see citing works
Plunkett, F. J., Franzese, O., Finney, H. M., Fletcher, J. M., Belaramani, L. L., Salmon, M., Dokal, I., Webster, D., Lawson, A. D. G., & Akbar, A. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.7710 · Cited by 222 · see citing works
Schönland, S. O., Lopez, C., Widmann, T., Zimmer, J., Bryl, E., Goronzy, J. J., & Weyand, C. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2233561100 · Cited by 216 · see citing works
Self-citationWege, H. (2002) · Nucleic Acids Research · doi:10.1093/nar/gng003 · Cited by 203 · see citing works
Goronzy, J. J., & Weyand, C. M. (2003) · Arthritis Research · doi:10.1186/ar974 · Cited by 199 · see citing works
Self-citationSchirmer, M., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.2.1018 · Cited by 191 · see citing works
Self-citationStepwise Differentiation of CD4 Memory T Cells Defined by Expression of CCR7 and CD27
Fritsch-Stork, R. D. E., Shen, X., Sims, G. P., Hathcock, K. S., Hodes, R. J., & Lipsky, P. E. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6489 · Cited by 184 · see citing works
Rufer, N., Migliaccio, M., Antonchuk, J., Humphries, R. K., Roosnek, E. E., & Lansdorp, P. M. (2001) · Blood · doi:10.1182/blood.v98.3.597 · Cited by 180 · see citing works
Marrone, A., Walne, A. J., Tamary, H., Masunari, Y., Kirwan, M., Beswick, R. W., Vulliamy, T., & Dokal, I. S. (2007) · Blood · doi:10.1182/blood-2006-12-062851 · Cited by 176 · see citing works
Sato, K., Niessner, A., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051062 · Cited by 175 · see citing works
Self-citationEctopic Lymphoid Organogenesis
Weyand, C. M., Kurtin, P. J., & Goronzy, J. J. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61751-8 · Cited by 151 · see citing works
Self-citationWill telomere erosion lead to a loss of T-cell memory?
Akbar, A. N., Beverley, P. C. L., & Salmon, M. (2004) · Nature Reviews Immunology · doi:10.1038/nri1440 · Cited by 135 · see citing works
Telomerase levels control the lifespan of human T lymphocytes
Röth, A., Yssel, H., Pène, J., Chavez, E. A., Schertzer, M., Lansdorp, P. M., Spits, H., & Luiten, R. M. (2003) · Blood · doi:10.1182/blood-2002-07-2015 · Cited by 133 · see citing works
Vulliamy, T., & Dokal, I. S. (2006) · Seminars in Hematology · doi:10.1053/j.seminhematol.2006.04.001 · Cited by 122 · see citing works
Reed, J. R., Vukmanovic-Stejic, M., Fletcher, J. M., Soares, M. V. D., Cook, J. E., Orteu, C. H., Jackson, S. E., Birch, K. E., Foster, G. R., Salmon, M., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040178 · Cited by 111 · see citing works
Colmegna, I., Diaz‐Borjon, A., Fujii, H., Schaefer, L., Goronzy, J. J., & Weyand, C. M. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23287 · Cited by 108 · see citing works
Self-citationLuiten, R. M., Pène, J., Yssel, H., & Spits, H. (2003) · Blood · doi:10.1182/blood-2002-07-2018 · Cited by 104 · see citing works
Knudson, M., Kulkarni, S., Ballas, Z. K., Bessler, M., & Goldman, F. (2005) · Blood · doi:10.1182/blood-2004-04-1673 · Cited by 82 · see citing works
T Cell Recognition and Killing of Vascular Smooth Muscle Cells in Acute Coronary Syndrome
Pryshchep, S., Sato, K., Goronzy, J. J., & Weyand, C. M. (2006) · Circulation Research · doi:10.1161/01.res.0000220649.10013.5c · Cited by 78 · see citing works
Self-citationThe role of DNA damage response proteins at telomeres—an “integrative” model
Slijepčević, P. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.038 · Cited by 73 · see citing works
T-cell-targeted therapies in rheumatoid arthritis
Weyand, C. M., & Goronzy, J. J. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0142 · Cited by 71 · see citing works
Self-citationPhosphorylation of H2AX at Short Telomeres in T Cells and Fibroblasts
Hao, L.-Y., Strong, M. A., & Greider, C. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403924200 · Cited by 71 · see citing works
Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes overexpressing hTERT
Röth, A., Baerlocher, G. M., Schertzer, M., Chavez, E. A., Dührsen, U., & Lansdorp, P. M. (2005) · Blood · doi:10.1182/blood-2004-10-4144 · Cited by 57 · see citing works
Therapy Insight: managing cardiovascular risk in patients with rheumatoid arthritis
Giles, J. T., Post, W. S., Blumenthal, R. S., & Bathon, J. M. (2006) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0178 · Cited by 51 · see citing works
p53-dependent integration of telomere and growth factor deprivation signals
Beliveau, A., Bassett, E., Lo, A. T., Garbe, J. C., Rubio, M. Á., Bissell, M. J., Campisi, J., & Yaswen, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700260104 · Cited by 38 · see citing works
Soares, M. V. D. (2003) · Blood · doi:10.1182/blood-2003-06-1791 · Cited by 34 · see citing works
T Cell Activation as Starter and Motor of Rheumatic Inflammation
Skapenko, A., Lipsky, P. E., & Schulze‐Koops, H. (2006) · Springer eBooks · doi:10.1007/3-540-29714-6_10 · Cited by 23 · see citing works
Telomere erosion: a new link between HLA DR4 and rheumatoid arthritis?
Salmon, M., & Akbar, A. N. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.05.002 · Cited by 16 · see citing works
Fudenberg, H. H., Goust, J. M., Vesole, D. H., & Salinas, C. F. (2009) · Gerontology · doi:10.1159/000212345 · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · see citing works
Self-citationAging of the Immune System. Mechanisms and Therapeutic Targets
Weyand, C. M., & Goronzy, J. J. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201602-095aw · Cited by 554 · see citing works
Self-citationInflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments
Zuo, L., Prather, E. R., Stetskiv, M., Garrison, D. E., Meade, J. R., Peace, T. I., & Zhou, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184472 · Cited by 545 · 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-citationAgeing and the telomere connection: An intimate relationship with inflammation
Zhang, J., Rane, G., Dai, X., Shanmugam, M. K., Arfuso, F., Samy, R. P., Lai, M. K. P., Kappei, D., Kumar, A. P., & Sethi, G. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.11.006 · Cited by 386 · see citing works
Rheumatoid arthritis and cardiovascular disease
Crowson, C. S., Liao, K. P., Davis, J. M., Solomon, D. H., Matteson, E. L., Knutson, K. L., Hlatky, M. A., & Gabriel, S. E. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.07.010 · Cited by 352 · see citing works
Naive T Cell Maintenance and Function in Human Aging
Goronzy, J. J., Fang, F., Cavanagh, M., Qi, Q., & Weyand, C. M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500046 · Cited by 348 · see citing works
Self-citationYang, Z., Fujii, H., Mohan, S. V., Goronzy, J. J., & Weyand, C. M. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130252 · Cited by 334 · see citing works
Self-citationSchoenmakers, E., Agostini, M., Mitchell, C., Schoenmakers, N., Papp, L., Rajanayagam, O., Padidela, R., Ceron-Gutierrez, L., Doffinger, R., Prevosto, C., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43653 · Cited by 315 · see citing works
Rheumatoid arthritis: From autoimmunity to synovitis and joint destruction
Boissier, M., Semerano, L., Challal, S., Saidenberg-Kermanac’h, N., & Falgarone, G. (2012) · Journal of Autoimmunity · doi:10.1016/j.jaut.2012.05.021 · Cited by 299 · see citing works
Goronzy, J. J., & Weyand, C. M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0970-0 · Cited by 292 · see citing works
Self-citationYang, Z., Shen, Y., Oishi, H., Matteson, E. L., Tian, L., Goronzy, J. J., & Weyand, C. M. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7151 · Cited by 275 · see citing works
Self-citationReversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells
Di Mitri, D., Azevedo, R. I., Henson, S. M., Libri, V., Riddell, N. E., Macaulay, R., Kipling, D., Soares, M. V. D., Battistini, L., & Akbar, A. N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100978 · Cited by 231 · see citing works
Immunometabolism in the development of rheumatoid arthritis
Weyand, C. M., & Goronzy, J. J. (2020) · Immunological Reviews · doi:10.1111/imr.12838 · Cited by 193 · see citing works
Self-citationMiao, C., Yang, Y., He, X., Li, X., Huang, C. Z., Huang, Y., Zhang, L., Lv, X., Jin, Y. J., & Li, J. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.04.002 · Cited by 201 · see citing works
Epidemiology of Rheumatoid Arthritis: Rheumatoid Arthritis and Mortality
Myasoedova, E., Davis, J. M., Crowson, C. S., & Gabriel, S. E. (2010) · Current Rheumatology Reports · doi:10.1007/s11926-010-0117-y · Cited by 190 · see citing works
Li, Y., Shen, Y., Jin, K., Wen, Z., Cao, W., Wu, B., Wen, R. M., Tian, L., Berry, G. J., Goronzy, J. J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.016 · Cited by 188 · see citing works
Self-citationHallmarks of the aging T‐cell system
Zhang, H., Weyand, C. M., & Goronzy, J. J. (2021) · FEBS Journal · doi:10.1111/febs.15770 · Cited by 177 · see citing works
Self-citationT-cell aging in rheumatoid arthritis
Weyand, C. M., Yang, Z., & Goronzy, J. J. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000011 · Cited by 164 · see citing works
Self-citationChen, L., Wu, B., Mo, L., Chen, H., Zhao, Y., Tan, T., Chen, L., Li, Y., Yao, P., & Tang, Y. (2023) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(23)00220-9 · Cited by 174 · see citing works
Healthy aging and disease: role for telomere biology?
Zhu, H., Belcher, M. D., & van der Harst, P. (2011) · Clinical Science · doi:10.1042/cs20100385 · Cited by 163 · see citing works
Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis.
Shao, L., Fujii, H., Colmegna, I., Oishi, H., Goronzy, J. J., & Weyand, C. M. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082251 · Cited by 159 · see citing works
Self-citationMethotrexate Inhibits NF‐κB Activity Via Long Intergenic (Noncoding) RNA–p21 Induction
Spurlock, C. F., Tossberg, J. T., Matlock, B. K., Olsen, N. J., & Aune, T. M. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38805 · Cited by 161 · see citing works
T-cell metabolism in autoimmune disease
Yang, Z., Matteson, E. L., Goronzy, J. J., & Weyand, C. M. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0542-4 · Cited by 156 · see citing works
Self-citationLaw, S. C., Street, S. E. A., Yu, C., Capini, C., Ramnoruth, S., Nel, H. J., van Gorp, E., Hyde, C., Lau, K., Pahau, H., et al. (2012) · Arthritis Research & Therapy · doi:10.1186/ar3848 · Cited by 155 · see citing works
Autophagy in Autoimmune Disease
Yang, Z., Goronzy, J., & Weyand, C. (2015) · Journal of molecular medicine · doi:10.1007/s00109-015-1297-8 · Cited by 141 · see citing works
Self-citationThe influence of ageing on the development and management of rheumatoid arthritis
Boots, A. M. H., Maier, A. B., Stinissen, P., Masson, P., Lories, R. J. U., & Keyser, F. D. (2013) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2013.92 · Cited by 148 · see citing works
Mechanisms of lung disease development in rheumatoid arthritis
Wang, D., Zhang, J., Lau, J., Wang, S., Taneja, V., Matteson, E. L., & Vassallo, R. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0275-x · Cited by 141 · see citing works
The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect?
Kordinas, V., Ioannidis, A., & Chatzipanagiotou, S. (2016) · Genes · doi:10.3390/genes7090060 · Cited by 139 · see citing works
Telomere dysfunction, autoimmunity and aging.
(2011) · Europe PMC (PubMed Central) · Cited by 138 · see citing works
Self-citationLi, Y., Shen, Y., Hohensinner, P. J., Ju, J., Wen, Z., Goodman, S. B., Zhang, H., Goronzy, J. J., & Weyand, C. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.013 · Cited by 138 · see citing works
Self-citationThe Janus Head of T Cell Aging – Autoimmunity and Immunodeficiency
Goronzy, J. J., Li, G., Yang, Z., & Weyand, C. M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00131 · Cited by 133 · see citing works
Self-citationThe Gracefully Aging Immune System
Boraschi, D., Aguado, M. T., Dutel, C., Goronzy, J. J., Louis, J. A., Grubeck‐Loebenstein, B., Rappuoli, R., & Giudice, G. D. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005624 · Cited by 133 · see citing works
Self-citationNewton, C. A., Kozlitina, J., Lines, J. R., Kaza, V., Torres, F., & Garcia, C. K. (2017) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2017.02.005 · Cited by 132 · see citing works
Developments in the scientific understanding of rheumatoid arthritis
Goronzy, J. J., & Weyand, C. M. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2758 · Cited by 130 · see citing works
Self-citationTelomere Shortening and Alzheimer’s Disease
Cai, Z., Yan, L., & Ratka, A. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8207-9 · Cited by 120 · see citing works
Rheumatoid Arthritis: A Role for Immunosenescence?
Lindström, T. M., & Robinson, W. H. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02965.x · Cited by 122 · see citing works
Telomeres and immunological diseases of aging.
Andrews, N. P., Fujii, H., Goronzy, J. J., & Weyand, C. M. (2010) · Gerontology · doi:10.1159/000268620 · Cited by 108 · see citing works
Self-citationVitamin D in rheumatoid arthritis—towards clinical application
Jeffery, L. E., Raza, K., & Hewison, M. (2015) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2015.140 · Cited by 116 · see citing works
Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging
Chalan, P., van den Berg, A., Kroesen, B., Brouwer, L., & Boots, A. M. H. (2015) · Current Aging Science · doi:10.2174/1874609808666150727110744 · Cited by 113 · see citing works
Rejuvenating the immune system in rheumatoid arthritis.
Weyand, C. M., Fujii, H., Shao, L., & Goronzy, J. J. (2009) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2009.180 · Cited by 112 · see citing works
Self-citationTelomeres, Telomerase and Ageing
Saretzki, G. C. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_9 · Cited by 114 · see citing works
Cellular and Molecular Mechanisms of Autoimmune Disease
Bolon, B. N. (2011) · Toxicologic Pathology · doi:10.1177/0192623311428481 · Cited by 111 · see citing works
Jose, S. S., Bendíčková, K., Kepák, T., Křenová, Z., & Frič, J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01078 · Cited by 105 · see citing works
Cell and cytokine imbalances in rheumatoid synovitis
Boissier, M. (2010) · Joint Bone Spine · doi:10.1016/j.jbspin.2010.08.017 · Cited by 103 · see citing works
Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression
Bauer, M. E. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00178-w · Cited by 102 · see citing works
McCray, C. J., & Agarwal, S. K. (2010) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2010.09.004 · Cited by 102 · see citing works
The telomere/telomerase system in autoimmune and systemic immune-mediated diseases
Georgin-Lavialle, S., Aouba, A., Mouthon, L., Londono-Vallejo, J. A., Lepelletier, Y., Gabet, A.-S., & Hermine, O. (2010) · Autoimmunity Reviews · doi:10.1016/j.autrev.2010.04.004 · Cited by 97 · see citing works
Chronic inflammation and aging: DNA damage tips the balance
Cavanagh, M. M., Weyand, C. M., & Goronzy, J. J. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.003 · Cited by 99 · see citing works
Self-citationImmune Aging and Rheumatoid Arthritis
Goronzy, J. J., Shao, L., & Weyand, C. M. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2010.03.001 · Cited by 99 · see citing works
Self-citationInterleukin-7 and Immunosenescence
Nguyen, V., Mendelsohn, A., & Larrick, J. W. (2017) · Journal of Immunology Research · doi:10.1155/2017/4807853 · Cited by 96 · see citing works
Telomerase and telomeres in aging theory and chronographic aging theory (Review)
Razgonova, M., Zakharenko, A., Golokhvast, K., Thanasoula, M., Sarandi, E., Nikolouzakis, K., Fragkiadaki, P., Tsoukalas, D., Spandidos, D., & Tsatsakis, A. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11274 · Cited by 89 · see citing works
Giant cell arteritis: immune and vascular aging as disease risk factors
Mohan, S., Liao, Y. J., Kim, J. W., Goronzy, J. J., & Weyand, C. M. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3358 · Cited by 95 · see citing works
Self-citationStress and immunosenescence: The role of telomerase
de Punder, K., Heim, C. C., Wadhwa, P. D., & Entringer, S. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.019 · Cited by 90 · see citing works
Gautam, S., Tolahunase, M., Kumar, U., & Dada, R. (2019) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-180875 · Cited by 87 · see citing works
IL-7– and IL-15–Mediated TCR Sensitization Enables T Cell Responses to Self-Antigens
Deshpande, P., Cavanagh, M., Saux, S. L., Singh, K., Weyand, C. M., & Goronzy, J. J. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201620 · Cited by 83 · see citing works
Self-citationStructural Biology of TelomerasePreprint
Wang, Y., Sušac, L., & Feigon, J. F. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032383 · Cited by 83 · see citing works
ERK-Dependent T Cell Receptor Threshold Calibration in Rheumatoid Arthritis
Singh, K., Deshpande, P., Pryshchep, S., Colmegna, I., Liarski, V. M., Weyand, C. M., & Goronzy, J. J. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901784 · Cited by 78 · see citing works
Self-citationDNA damage, metabolism and aging in pro-inflammatory T cells
Li, Y., Goronzy, J. J., & Weyand, C. M. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.027 · Cited by 79 · see citing works
Self-citationAssociation of nutraceutical supplements with longer telomere length
Tsoukalas, D., Fragkiadaki, P., Docea, A. O., Alegakis, A. K., Sarandi, E., Vakonaki, E., Salataj, E., Kouvidi, E., Nikitovic, D., Kovatsi, L., et al. (2019) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2019.4191 · Cited by 76 · see citing works
Mechanisms of immunosenescence: lessons from models of accelerated immune aging
Saux, S. L., Weyand, C. M., & Goronzy, J. J. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06297.x · Cited by 75 · see citing works
Self-citationSuzuki, M., Jagger, A. L., Konya, C., Shimojima, Y., Pryshchep, S., Goronzy, J. J., & Weyand, C. M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200122 · Cited by 74 · see citing works
Self-citationDNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis.
Shao, L., Goronzy, J. J., & Weyand, C. M. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000096 · Cited by 69 · see citing works
Self-citationMatson, S. M., Lee, J. S., & Eickelberg, O. (2020) · European Respiratory Journal · doi:10.1183/13993003.02533-2020 · Cited by 68 · see citing works
The interplay between obesity, immunosenescence, and insulin resistance
Shimi, G., Sohouli, M. H., Ghorbani, A., Shakery, A., & Zand, H. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00414-7 · Cited by 73 · see citing works
Redox-sensitive signaling in inflammatory T cells and in autoimmune disease
Weyand, C. M., Shen, Y., & Goronzy, J. J. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.03.004 · Cited by 66 · see citing works
Self-citationRheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes
Rhead, B. L., Holingue, C., Cole, M. B., Shao, X., Quach, H., Quach, D. L., Shah, K., Sinclair, E., Graf, J., Link, T. M., et al. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39952 · Cited by 65 · see citing works
Immunosenescence, Aging, and Systemic Lupus Erythematous
Montoya-Ortiz, G. (2013) · Autoimmune Diseases · doi:10.1155/2013/267078 · Cited by 65 · see citing works
Patrick, M. S., & Weng, N. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2019.103989 · Cited by 62 · see citing works
Telomerase: Key regulator of inflammation and cancer
Wu, L., Fidan, K., Um, J., & Ahn, K. S. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104726 · Cited by 61 · see citing works
Perdaens, O., & Pesch, V. V. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.811518 · Cited by 59 · see citing works
Migration and homeostasis of regulatory T cells in rheumatoid arthritis
Kotschenreuther, K., Yan, S., & Kofler, D. M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.947636 · Cited by 57 · see citing works
Bolton, C., & Smith, P. A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.005 · Cited by 57 · see citing works
Association between shorter leukocyte telomeres and multiple sclerosis
Habib, R., Ocklenburg, S., Hoffjan, S., Haghikia, A., Epplen, J. T., & Arning, L. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577187 · Cited by 52 · see citing works
Systemic Sclerosis Association with Malignancy
Lepri, G., Catalano, M., Bellando-Randone, S., Pillozzi, S., Giommoni, E., Giorgione, R., Botteri, C., Matucci‐Cerinic, M., Antonuzzo, L., & Guiducci, S. (2022) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-022-08930-4 · Cited by 53 · see citing works
Immune Aging in Rheumatoid Arthritis
Weyand, C. M., & Goronzy, J. J. (2025) · Arthritis & Rheumatology · doi:10.1002/art.43105 · Cited by 56 · see citing works
Self-citationImmunosenescence and rheumatoid arthritis: Does telomere shortening predict impending disease?
Costenbader, K. H., Prescott, J., Zee, R. Y. L., & Vivo, I. D. (2011) · Autoimmunity Reviews · doi:10.1016/j.autrev.2011.04.034 · Cited by 52 · see citing works
Su, Q., Jing, J., Li, W., Ma, J., Zhang, X., Wang, Z., Zhou, Z., Dai, L., & Shao, L. (2019) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.02.007 · Cited by 51 · see citing works
Self-citationTelomere length and telomerase activity in osteoporosis and osteoarthritis (Review)
Fragkiadaki, P., Nikitovic, D., Kalliantasi, K., Sarandi, E., Thanasoula, M., Stivaktakis, P. D., Nepka, C., Spandidos, D. A., Theodoros, T., & Tsatsakis, A. M. (2019) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2019.8370 · Cited by 50 · see citing works
Gautam, S., Kumar, U., Kumar, M., Rana, D., & Dada, R. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.03.004 · Cited by 53 · see citing works
Telomerase and Primary T Cells: Biology and Immortalization for Adoptive Immunotherapy
Barsov, E. V. (2011) · Immunotherapy · doi:10.2217/imt.10.107 · Cited by 49 · see citing works
Zhao, J., Nguyen, L. N. T., Nguyen, L. N., Dang, X., Cao, D., Khanal, S., Schank, M., Thakuri, B. K. C., Ogbu, S. C., Morrison, Z. D., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02531 · Cited by 47 · see citing works
Telomeres: New players in immune-mediated inflammatory diseases?
Heba, A.-C., Toupance, S., Arnone, D., Peyrin‐Biroulet, L., Bénétos, A., & Ndiaye, N. C. (2021) · Journal of Autoimmunity · doi:10.1016/j.jaut.2021.102699 · Cited by 46 · see citing works
Zhao, J., Dang, X., Zhang, P., Nguyen, L. N., Cao, D., Wang, L., Wu, X., Morrison, Z. D., Zhang, Y., Zhansheng, J., et al. (2018) · Cell Discovery · doi:10.1038/s41421-018-0015-4 · Cited by 46 · see citing works
Pulmonary Complications of Rheumatoid Arthritis
Farquhar, H. J., Vassallo, R., Edwards, A. L., & Matteson, E. L. (2019) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0039-1683995 · Cited by 46 · see citing works
Regulation of telomerase activity by apparently opposing elements
Liu, J., Chen, S., Cong, Y.-S., Nicholls, C., Zhou, S.-F., Tao, Z., & Li, H. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.03.002 · Cited by 45 · see citing works
Progress in Human andTetrahymenaTelomerase Structure Determination
Chan, H., Wang, Y., & Feigon, J. F. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-062215-011140 · Cited by 45 · see citing works
T 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-citationLymphopenia in primary Sjögren’s syndrome is associated with premature aging of naïve CD4+ T cells
Fessler, J., Fasching, P., Raicht, A., Hammerl, S., Weber, J., Lackner, A., Hermann, J., Dejaco, C., Graninger, W. B., Schwinger, W., et al. (2020) · Lara D. Veeken · doi:10.1093/rheumatology/keaa105 · Cited by 44 · see citing works
Fernandes, S. G., Dsouza, R., & Khattar, E. (2021) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2021.103633 · Cited by 42 · see citing works
Liu, S., Nong, W., Ji, L., Zhuge, X., Wei, H., Luo, M., Zhou, L., Chen, S., Zhang, S., Lei, X., et al. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112132 · Cited by 43 · see citing works
K-RAS GTPase- and B-RAF kinase–mediated T-cell tolerance defects in rheumatoid arthritis
Singh, K., Deshpande, P., Li, G., Yu, M., Pryshchep, S., Cavanagh, M., Weyand, C. M., & Goronzy, J. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117640109 · Cited by 40 · see citing works
Self-citationNeuroendocrine and viral correlates of premature immunosenescence
Bauer, M. E., Wieck, A., Petersen, L. E., & Baptista, T. S. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12786 · Cited by 41 · 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
Self-citationWatanabe, R., Fujii, H., Shirai, T., Saito, S., Ishii, T., & Harigae, H. (2014) · European Journal of Immunology · doi:10.1002/eji.201344248 · Cited by 38 · see citing works
Self-citationHaematopoietic stem and progenitor cells in rheumatoid arthritis.
Colmegna, I., & Weyand, C. M. (2011) · Rheumatology · doi:10.1093/rheumatology/keq298 · Cited by 37 · see citing works
Self-citationThe central role of DNA damage in immunosenescence
Kell, L., Simon, A. K., Alsaleh, G., & Cox, L. S. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1202152 · Cited by 38 · see citing works
Adaptive immunity and atherosclerosis: aging at its crossroads
Snijckers, R., & Foks, A. C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1350471 · Cited by 39 · see citing works
Cao, D., Zhao, J., Nguyan, L. N., Nguyen, L. N., Khanal, S., Dang, X., Schank, M., Thakuri, B. K. C., Wu, X. Y., Morrison, Z. D., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01152 · Cited by 35 · see citing works
Nguyen, L. N., Zhao, J., Cao, D., Dang, X., Wang, L., Lian, J., Zhang, Y., Jia, Z., Wu, X. Y., Morrison, Z. D., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0897-y · Cited by 34 · see citing works
- Authors
- Fujii, H., Shao, L., Colmegna, I., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Emory University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-03-17
- Volume
- 106
- Issue
- 11
- Pages
- 4360-4365
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2657451
- OpenAlex
- W2067557887
- Cited by
- 172
- References
- 45
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 10 · 2021: 7 · 2020: 16 · 2019: 15 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 11 · 2014: 8 · 2013: 13 · 2012: 11
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Institute on Aging (R01AG015043, R01AG15043)
- National Heart, Lung, and Blood Institute (R01HL117913)
- National Eye Institute (R01EY011916)
- National Institute of Allergy and Infectious Diseases (R01AI044142, R01 AI57266, R01AI44142, R01AI108906, R56AI044142, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- rheumatoid arthritis, human telomerase reverse transcriptase, hTERT, T cell senescence, naive CD4+ T cells, memory T cells, T cell apoptosis, clonal expansion, lymphopenia, T cell receptor stimulation, hematopoietic stem cells, joint inflammation, telomere length
- MeSH terms
- Arthritis, Rheumatoid, Hematopoietic Stem Cells, Humans, Immunologic Memory, T-Lymphocytes, Down-Regulation, Case-Control Studies, Telomere, Cellular Senescence, Telomerase
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