The telomere/telomerase system in autoimmune and systemic immune-mediated diseases
Abstract
Telomeres are specialized nucleoproteic structures that cap and protect the ends of chromosomes. They can be elongated by the telomerase enzyme, but in telomerase negative cells, telomeres shorten after each cellular division because of the end replicating problem. This phenomenon leads ultimately to cellular senescence, conferring to the telomeres a role of biological clock. Oxidative stress, inflammation and increased cell renewal are supplementary environmental factors that accelerate age-related telomere shortening. Similar to other types of DNA damage, very short/dysfunctional telomeres activate a DNA response pathway leading to different outcomes: DNA repair, cell senescence or apoptosis. During the last 10 years, studies on the telomere/telomerase system in autoimmune and/or systemic immune-mediated diseases have revealed its involvement in relevant physiopathological processes. Here, we present a literature review of telomere and telomerase homeostasis in systemic inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis and granulomatous diseases. The available data indicate that both telomerase activity and telomere length are modified in various systemic immune-mediated diseases and appear to be connected with premature immunosenescence. Studies on the telomere/telomerase system open new research avenues for the basic understanding and for therapeutic approaches of these pathologies.
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Defective repair of DNA lesions and uncapped telomeres create genomic stress in aging T cells.
“Also, leakiness in repairing DNA lesions and uncapped telomeres imposes genomic stress.”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [63]
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“Telomeres are located at the ends of chromosomes, are composed of repeated DNA sequences and ensure that each DNA replication cycle has been completed [93].”
BackgroundInfluentialAdverse childhood experience and rheumatic diseases
Luiz, A. P. L., Antico, H. D. A., Skare, T. L., Boldt, A. B. W., & Nisihara, R. (2018) · Clinical Rheumatology · doi:10.1007/s10067-018-4200-5 · Cited by 26 · see citing works
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“Shorter telomeres, caused by DNA damage to the telomere region of the genome, may also contribute to the pathogenesis of autoimmunity and the production of ANA [22, 23].”
BackgroundHernández‐González, F., Pietrocola, F., Cameli, P., Bargagli, E., Prieto‐González, S., Cruz, T., Mendoza, N., Rojas, M. M., Serrano, M., Agustí, A. G. N., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147554 · Cited by 18 · see citing works
“Other theories suggests that autoimmune conditions are marked by an inflammatory cascade instigated by immune cells targeting tissues, potentially releasing free radicals that could harm telomeres and expedite their degradation, thereby contributing to a self-loop [112].”
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Aging in Fabry Disease: Role of Telomere Length, Telomerase Activity, and Kidney Disease
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Ectopic expression of telomerase safely increases health span and life span
Mendelsohn, A. R., & Larrick, J. W. (2012) · Rejuvenation Research · doi:10.1089/rej.2012.1359 · Cited by 14 · see citing works
“…relates to the critical question of whether sufficient clinical benefit could result from ectopic telomerase expression in human aging and in diseases associated with shortened telomeres such as autoimmune diseases, 13 chronic obstructive pulmonary disease (COPD), 14 and cardiovascular disease.”
Invernizzi, P., Bernuzzi, F., Lleò, A., Pozzoli, V., Bignotto, M., Zermiani, P., Crosignani, A., Battezzati, P. M., Zuin, M. G., Podda, M., et al. (2014) · Digestive and Liver Disease · doi:10.1016/j.dld.2013.11.008 · Cited by 14 · see citing works
Pavlaki, K. I., Kastrinaki, M.-C., Klontzas, M., Velegraki, M., Mavroudi, I., & Papadaki, H. Α. (2011) · Haematologica · doi:10.3324/haematol.2011.053983 · Cited by 14 · see citing works
“The χ2 test was used to determine the homogeneity of the populations regarding the age (P=0.493) and sex (P=0.968) distribution, as well as to determine differences in the proportion of patients and controls displaying telomerase activity or hTERT expression in PBMCs.”
BackgroundInfluentialWang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H., Li, L., Ding, K., Wang, T., Wang, H., et al. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.8014 · Cited by 14 · see citing works
“sclerosis and Type I diabetes, above all there are telomere shortening (35-38).”
BackgroundLópez‐Doriga, A., Valle, L., Alonso, M. H., Aussó, S., Closa, A., Sanjuán, X., Barquero, D., Rodríguez‐Moranta, F., Pamplona, R. S., & Moreno, V. R. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.06.010 · Cited by 18 · see citing works
“Other studies also have associated the telomere complex with autoimmune or inflammatory pathways by different mechanisms [45, 46].”
BackgroundSustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus
Perez-Bercoff, D., Laude, H., Lemaire, M., Hunewald, O. E., Thiers, V., Vignuzzi, M., Blanc, H., Poli, A., Amoura, Z., Caval, V., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-87024-1 · Cited by 13 · see citing works
Picarelli, M. M. C., Danzmann, L. C., Grün, L. K., da Rosa‐Junior, N. T., Lavandovsky, P., Guma, F. T. C. R., Stein, R. T., Barbé‐Tuana, F. M., & Jones, M. H. (2017) · Pediatric Rheumatology · doi:10.1186/s12969-017-0165-1 · Cited by 13 · see citing works
“main environmental factors associated to telomere shortening [9] and impairment in endothelial function”
BackgroundSkamra, C., Romero‐Díaz, J., Sandhu, A. T., Huang, Q.-Q., Lee, J. J., Pearce, W. B., McPherson, D. D., Sutton-Tyrrell, K., Pope, R. M., & Ramsey‐Goldman, R. (2013) · Lara D. Veeken · doi:10.1093/rheumatology/kes424 · Cited by 13 · see citing works
Banaszak, L. G., Smith-Simmer, K. J., Shoger, K., Lovrien, L., Malik, A., Sandbo, N. K., Sultan, S., Guzy, R. D., Lowery, E. M., & Churpek, J. E. (2023) · Respiratory Medicine · doi:10.1016/j.rmed.2023.107464 · Cited by 12 · see citing works
Dai, Y., Tai, Y., Chang, Y.-T., Chen, T., & Chen, M. (2021) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000920 · Cited by 12 · see citing works
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Ye, M., Wang, Y., & Zhan, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.998102 · Cited by 11 · see citing works
Connecting the Dots: Telomere Shortening and Rheumatic Diseases
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Tekaya, A. B., Hannech, E., Saidane, O., Rouached, L., Bouden, S., Tekaya, R., Mahmoud, I., & ABDELMOULA, L. (2022) · BMC Rheumatology · doi:10.1186/s41927-022-00308-5 · Cited by 10 · see citing works
“Telomere shortening is also observed in RA due to the systemic inflammation and the effect of auto-antibodies [33].”
BackgroundTelomere length and multiple sclerosis: a Mendelian randomization study
Ma, Y., Wang, M., Chen, X., Ruan, W., Yao, J., & Lian, X. (2022) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2098737 · Cited by 10 · see citing works
“Individuals with longer leukocyte telomeres may have a stronger immune response owing to increased proliferative potential [26,27].”
BackgroundQi, A., Zhou, H., Zhou, Z., Huang, X., Ma, L., Wang, H., Yang, Y., Zhang, D., Li, H., Ren, R., et al. (2012) · Journal of Clinical Immunology · doi:10.1007/s10875-012-9848-z · Cited by 10 · see citing works
Wang, B., Xiong, Y., Ren, L., Zhang, J., & Zhang, S. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1251 · Cited by 8 · see citing works
“9 One study also shows that telomeres and telomerase play crucial roles in T ‐ cell differentiation, aging, and diseases.”
BackgroundTesovnik, T., Kovač, J., Hovnik, T., Kotnik, P., Battelino, T., & Podkrajšek, K. T. (2015) · Slovenian Journal of Public Health · doi:10.1515/sjph-2015-0011 · Cited by 9 · see citing works
“Inflammation is present in many chronic and autoimmune diseases, such as cardiovascular diseases, rheumatoid arthritis, systemic lupus erythematosus, type 1 and 2 diabetes (9, 11).”
BackgroundSenescence- and Immunity-Related Changes in the Central Nervous System: A Comprehensive Review
Feng, H., Li, J., Wang, H., Wei, Z., & Feng, S. (2024) · Aging and Disease · doi:10.14336/ad.2024.0755 · Cited by 10 · see citing works
Zhang, J., Wei, M., Lü, R., Du, G., & Zhou, G. (2015) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.12399 · Cited by 8 · see citing works
Accelerated telomere shortening in β-thalassemia/HbE patients
Chaichompoo, P., Pattanapanyasat, K., Winichagoon, P., Fucharoen, S., & Svasti, S. (2015) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2015.01.003 · Cited by 8 · see citing works
Laish, I., Katz, H., Stein, A., Liberman, M., Naftali, T., Kitay‐Cohen, Y., Biron‐Shental, T., Konikoff, F. M., & Amiel, A. (2015) · Digestive and Liver Disease · doi:10.1016/j.dld.2015.05.002 · Cited by 7 · see citing works
“Thus, many studies have observed that accelerated telomere loss is a common feature of systemic autoimmune disease, such as systemic lupus erythematosus or rheumatoid arthritis [37], and local or systemic fibrotic conditions, such as scleroderma [38], idiopathic pulmonary fibrosis [39] and cirrhosis [32, 36].”
BackgroundPortillo, A. M., & Peláez-Rodríguez, C. (2021) · Mathematical Medicine and Biology A Journal of the IMA · doi:10.1093/imammb/dqab004 · Cited by 7 · see citing works
Liu, M., Fan, Y., Ni, N., Yu, T., Mao, Z., Huang, H.-Y., Zhang, J., Tang, Y., He, H., Meng, F. J., et al. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14577 · Cited by 6 · see citing works
Liu, X., Yuan, J., Liu, S., Wang, X., Tang, M., Meng, X., Li, Y., Chai, Y., Wang, Y., Tian, G., et al. (2024) · Clinical Endocrinology · doi:10.1111/cen.15004 · Cited by 5 · see citing works
Bridges, J. M., Chung, K. W., Martz, C. D., Smitherman, E. A., Drenkard, C., Wu, C., Lin, J., Lim, S. S., & Chae, D. H. (2022) · ACR Open Rheumatology · doi:10.1002/acr2.11411 · Cited by 5 · see citing works
The Relevance of Chronological and Biological Aging in the Progression of Multiple Sclerosis
Mulero, P., Chavarría‐Miranda, A., & Téllez, N. (2025) · Healthcare · doi:10.3390/healthcare13202619 · Cited by 4 · see citing works
Liao, Y., Zhang, X., Tao, S., Wang, S., Huang, Q., Tang, P., Tang, A., Yang, P., & Yang, G. (2024) · American Journal of Rhinology and Allergy · doi:10.1177/19458924241269686 · Cited by 4 · see citing works
“18 In patients with system lupus erythematosus, the activity of TERT is higher in immune cells, especially in B cells, than that in HCs. 19 Our data is consistent with these previous studies by showing higher TERT activity in CD4 + T cells in AR patients.”
Integration of Telomere Length Dynamics into Systems Biology Framework: A Review
Nersisyan, L. (2016) · Gene Regulation and Systems Biology · doi:10.4137/grsb.s39836 · Cited by 4 · see citing works
Tang, X., Hu, J., Fan, X., Su, H., Li, M., Zhang, L., & Ma, D. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00541-9 · Cited by 4 · see citing works
“Telomere length is significantly reduced in autoimmune diseases like SS [121], we speculate that telomere maintenance may represent a promising therapeutic target.”
Gao, J., He, J., Zhao, W., Cui, J., Zhang, Q., Yang, P., Yang, F., Chen, Y., & Zhang, M. (2025) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaf118 · Cited by 3 · see citing works
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Benedittis, G. D., Cela, E., Morgante, C., Latini, A., D’Antonio, A., Fatica, M., Mori, G., Conigliaro, P., Ciccacci, C., Novelli, G., et al. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01952-0 · Cited by 2 · see citing works
“Literature data on other autoimmune rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythema-tosus, have already described an alteration of the telomere region [7, 10, 24].”
Telomere length as a marker of biological age in paediatric multiple sclerosis
Jacques, K., Race, J. A., Goyne, C., Fair, A. E., Schuette, A., Yang, J. H., Caillier, S. J., Aaen, G. S., Abrams, A. W., Benson, L. A., et al. (2026) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2025-336736 · Cited by 2 · see citing works
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“Interestingly, aberrant, inflammationdriven T-cell proliferative responses in association with premature telomere loss resulting in age-inappropriate T-cell senescence and disturbed T-cell homeostasis have been described in patients with autoimmune and systemic immune-mediated diseases (33).”
BackgroundRethinking the Origin of Chronic Diseases
Shoja, M. M., Tubbs, R. S., Ghaffari, A., Loukas, M., & Agutter, P. S. (2012) · BioScience · doi:10.1525/bio.2012.62.5.8 · Cited by 2 · see citing works
Identification of telomere-related gene subtypes and prognostic signatures in osteosarcoma
Song, Z., Yu, W., & Yin, X. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1545913 · Cited by 1 · see citing works
Extracellular vesicles for delivery of functional telomerase
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Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort
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“As shorter TL has been associated with higher risk of age-related disease and early mortality (Arbeev et al., 2020; Georgin-Lavialle et al., 2010; Haycock et al., 2014; Wang et al., 2018), persistently shorter TL throughout lifespan could indicate that individuals with ASD have higher risk of…”
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The S100A7 nuclear interactors in autoimmune diseases: a coevolutionary study in mammals
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Biological Ageing Research in Systemic Sclerosis: Time to Grow up?
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Prediction of Psoriasis from Gene Expression Profiling Using Penalized Logistic Regression Model
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“Inflammation accelerates cellular senescence due to the shortening of telomere length, and recent studies have indicated that telomere length plays a role in the pathogenesis of various autoimmune diseases (19, 20) .”
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“What’s more, Telomere shortening in lymphocytes is considered to represent the aging of the immune system and may predispose to autoimmune responses [16].”
Moura, D. (2013) · doi:10.70675/aa8d9d32zc265z4525z833dzb5a1ddfbb990
“rhumatoïde et des maladies granulomateuses [81, 82].”
Senescence of the immune system in SLE: Pathogenic mechanisms and therapeutic implications
Jiang, X., Liang, Z., Zhao, C., Li, F., Su, Q., Wang, Y., Zhang, S., & Cheng, T. (2026) · Autoimmunity Reviews · doi:10.1016/j.autrev.2026.104152
- Authors
- Georgin-Lavialle, S., Aouba, A., Mouthon, L., Londono-Vallejo, J. A., Lepelletier, Y., Gabet, A.-S., & Hermine, O.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Université Paris Cité (FR)
- Corresponding author
- Hermine, Olivier
- Venue
- Autoimmunity Reviews
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 9
- Issue
- 10
- Pages
- 646-651
- ISSN
- 1568-9972 (ISSN-L)
- OpenAlex
- W2154984881
- Cited by
- 97
- References
- 46
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 11 · 2023: 4 · 2022: 12 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 6
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autoimmunity Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- telomeres, telomerase, telomere length, cellular senescence, immunosenescence, autoimmune disease, systemic lupus erythematosus, rheumatoid arthritis, granulomatous disease, telomere dysfunction, DNA damage response, oxidative stress, inflammation
- MeSH terms
- Animals, Autoimmune Diseases, DNA Damage, Enzyme Activation, Humans, Telomere, Cellular Senescence, Apoptosis, Telomerase, Aging, Premature
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