Running Against Time: The Effects of Endurance Exercise on Telomere Dynamics and Longevity
DOI:
https://doi.org/10.58445/rars.3200Keywords:
Telomere Attrition, Cellular Biology, Cellular Aging, Endurance Running, Telomere Biotechnology, LongevityAbstract
Telomere attrition, recognized as the hallmark of aging, is linked to an increased risk of certain negative health outcomes such as cardiovascular disease, metabolic dysfunction, and neurodegenerative disease. Regular endurance exercise is one potential solution to lengthening telomeres; however, since high-intensity endurance exercise causes oxidative stress, the direct impact of running on telomere dynamics remains unclear. This review synthesizes current literature on leukocyte telomere length (LTL) in endurance runners and evaluates emerging biotechnological interventions targeting telomere attrition. In addition, it examines cross-sectional and longitudinal studies comparing LTLs in trained endurance athletes, sedentary individuals, and age-matched controls. From analyzing different studies, evidence indicates that habitual aerobic exercise, particularly running, is associated with longer LTL and delayed biological aging, though excessive high-intensity training may accelerate telomere shortening. Other solutions to telomere shortening can be mitigated through various biotechnological approaches, including telomerase activators (e.g., TA-65), telomerase gene therapy, and senolytics. Although these approaches have been recognized for reducing senescent cells and extending telomere lengths, concerns regarding cancer risk and long-term safety persist. Overall, the findings suggest that endurance running slows biological aging by attenuating age-related telomere attrition. Further integrating exercise with emerging telomere-targeted therapies offers complementary strategies for promoting healthspan.
References
Armanios, M. (2013). Telomeres and age-related disease: how telomere biology informs clinical paradigms. Journal of Clinical Investigation, 123(3), 996–1002. https://doi.org/10.1172/jci66370
Arsenis, N. C., You, T., Ogawa, E. F., Tinsley, G. M., & Zuo, L. (2017). Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget, 8(27). https://doi.org/10.18632/oncotarget.16726
Balan, E., Decottignies, A., & Deldicque, L. (2018). Physical Activity and Nutrition: Two Promising Strategies for Telomere Maintenance? Nutrients, 10(12), 1942. https://doi.org/10.3390/nu10121942
Baliou, S., Spanakis, M., Apetroaei, M.-M., Ioannou, P., Fragkiadaki, P., Fragkiadoulaki, I., Renieri, E., Vakonaki, E., Tzatzarakis, M., Nosyrev, A., & Tsatsakis, A. (2025). The impact of exercise on telomere length dynamics: Molecular mechanisms and implications in athletes (Review). World Academy of Sciences Journal, 7(4), 1–12. https://doi.org/10.3892/wasj.2025.344
Bernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., & Blasco, M. A. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Molecular Medicine, 4(8), 691–704. https://doi.org/10.1002/emmm.201200245
BioRender. (2025). Biorender.com. https://app.biorender.com/biorender-templates/details/t-5e3c3e382a90ac00861a494b-telomere-shortening
Blackmon, C. M., Tucker, L. A., Bailey, B. W., & Davidson, L. E. (2023). Time Spent Jogging/Running and Biological Aging in 4458 U.S. Adults: An NHANES Investigation. International Journal of Environmental Research and Public Health, 20(19), 6872. https://doi.org/10.3390/ijerph20196872
Chen, M., Wang, Z., Xu, H., Teng, P., Li, W., & Ma, L. (2024). Association between modifiable lifestyle factors and telomere length: a univariable and multivariable Mendelian randomization study. Journal of Translational Medicine, 22(1). https://doi.org/10.1186/s12967-024-04956-8
Cherkas, L. F., Hunkin, J. L., Kato, B. S., Richards, J. B., Gardner, J. P., Surdulescu, G. L., Kimura, M., Lu, X., Spector, T. D., & Aviv, A. (2008). The association between physical activity in leisure time and leukocyte telomere length. Archives of Internal Medicine, 168(2), 154–158. https://doi.org/10.1001/archinternmed.2007.39
Crocco, P., De Rango, F., Dato, S., La Grotta, R., Maletta, R., Bruni, A. C., Passarino, G., & Rose, G. (2023). The Shortening of Leukocyte Telomere Length Contributes to Alzheimer’s Disease: Further Evidence from Late-Onset Familial and Sporadic Cases. Biology, 12(10), 1286. https://doi.org/10.3390/biology12101286
de Jesus, B. B., Schneeberger, K., Vera, E., Tejera, A., Harley, C. B., & Blasco, M. A. (2011). The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell, 10(4), 604–621. https://doi.org/10.1111/j.1474-9726.2011.00700.x
de Lange, T. (2002). Protection of mammalian telomeres. Oncogene, 21(4), 532–540. https://doi.org/10.1038/sj.onc.1205080
Deng, Y., Li, Q., Zhou, F., Li, G., Liu, J., Jialan Lv, Li, L., & Chang, D. (2022). Telomere length and the risk of cardiovascular diseases: A Mendelian randomization study. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.1012615
Denham, J., Nelson, C. P., O’Brien, B. J., Nankervis, S. A., Denniff, M., Harvey, J. T., Marques, F. Z., Codd, V., Zukowska-Szczechowska, E., Samani, N. J., Tomaszewski, M., & Charchar, F. J. (2013). Longer Leukocyte Telomeres Are Associated with Ultra-Endurance Exercise Independent of Cardiovascular Risk Factors. PLoS ONE, 8(7), e69377. https://doi.org/10.1371/journal.pone.0069377
Denham, J., O’Brien, B. J., Prestes, P. R., Brown, N. J., & Charchar, F. J. (2016). Increased expression of telomere-regulating genes in endurance athletes with long leukocyte telomeres. Journal of Applied Physiology, 120(2), 148–158. https://doi.org/10.1152/japplphysiol.00587.2015
Denham, J., & Sellami, M. (2021). Exercise training increases telomerase reverse transcriptase gene expression and telomerase activity: A systematic review and meta-analysis. Ageing Research Reviews, 70, 101411. https://doi.org/10.1016/j.arr.2021.101411
Eppard, M., Passos, J. F., & Victorelli, S. (2023). Telomeres, cellular senescence, and aging: past and future. Biogerontology. https://doi.org/10.1007/s10522-023-10085-4
Harrison, C. (2012). Telomerase gene therapy increases longevity. Nature Reviews Drug Discovery, 11(7), 518–518. https://doi.org/10.1038/nrd3795
Haseltine, W. (2024, August 21). Extending Telomere Length? A Look At Current Strategies - William A. Haseltine PhD. William A. Haseltine PhD. https://www.williamhaseltine.com/extending-telomere-length-a-look-at-current-strategies
Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., Kellogg, T. A., Khosla, S., Koerber, D. M., Lagnado, A. B., Lawson, D. K., LeBrasseur, N. K., Lerman, L. O., McDonald, K. M., McKenzie, T. J., & Passos, J. F. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47. https://doi.org/10.1016/j.ebiom.2019.08.069
Ibraheem Shelash Al-Hawary, S., Ali Alzahrani, A., Ghaleb Maabreh, H., Abed Jawad, M., Alsaadi, S. B., Kareem Jabber, N., Alawadi, A., Alsalamy, A., & Alizadeh, F. (2024). The association of metabolic syndrome with telomere length as a marker of cellular aging: a systematic review and meta-analysis. Frontiers in Genetics, 15. https://doi.org/10.3389/fgene.2024.1390198
Jaijyan, D. K., Selariu, A., Cruz-Cosme, R., Tong, M., Yang, S., Stefa, A., Kekich, D., Sadoshima, J., Herbig, U., Tang, Q., Church, G., Parrish, E. L., & Zhu, H. (2022). New intranasal and injectable gene therapy for healthy life extension. Proceedings of the National Academy of Sciences, 119(20). https://doi.org/10.1073/pnas.2121499119
Kim, J. J., Ahn, A., Ying, J., Hickman, E., & Ludlow, A. T. (2023). Exercise as a Therapy to Maintain Telomere Function and Prevent Cellular Senescence. Exercise and Sport Sciences Reviews, 51(4), 150–160. https://doi.org/10.1249/jes.0000000000000324
Kirkland, J. L., & Tchkonia, T. (2020). Senolytic drugs: from discovery to translation. Journal of Internal Medicine, 288(5), 518–536. https://doi.org/10.1111/joim.13141
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023). Hallmarks of aging: An expanding universe. Cell, 186(2), 243–278. https://doi.org/10.1016/j.cell.2022.11.001
MD, D. K. (2021, February 24). Lowering cholesterol protects your heart and brain, regardless of your age. Harvard Health. https://www.health.harvard.edu/blog/lowering-cholesterol-protects-your-heart-and-brain-regardless-of-your-age-2021022421978
Paul, L. (2011). Diet, nutrition and telomere length. The Journal of Nutritional Biochemistry, 22(10), 895–901. https://doi.org/10.1016/j.jnutbio.2010.12.001
Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., Hagler, M., Jurk, D., Smith, L. A., Casaclang-Verzosa, G., Zhu, Y., Schafer, M. J., Tchkonia, T., Kirkland, J. L., & Miller, J. D. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 15(5), 973–977. https://doi.org/10.1111/acel.12458
Sánchez-González, J. L., Sánchez-Rodríguez, J. L., Varela-Rodríguez, S., González-Sarmiento, R., Rivera-Picón, C., Juárez-Vela, R., Tejada-Garrido, C. I., Martín-Vallejo, J., & Navarro-López, V. (2024). Effects of Physical Exercise on Telomere Length in Healthy Adults: Systematic Review, Meta-Analysis, and Meta-Regression. JMIR Public Health and Surveillance, 10(1), e46019. https://doi.org/10.2196/46019
Singaravelu, G., B Harley, C., M Raffaele, J., Sudhakaran, P., & Suram, A. (2021). Double-Blind, Placebo-Controlled, Randomized Clinical Trial Demonstrates Telomerase Activator TA-65 Decreases Immunosenescent CD8+CD28- T Cells in Humans. OBM Geriatrics, 05(02), 1–1. https://doi.org/10.21926/obm.geriatr.2102168
Song, S., Lee, E., & Kim, H. (2022). Does Exercise Affect Telomere Length? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicina, 58(2), 242. https://doi.org/10.3390/medicina58020242
Sousa, C. V., Aguiar, S. S., Santos, P. A., Barbosa, L. P., Knechtle, B., Nikolaidis, P. T., Deus, L. A., Sales, M. M., Rosa, E. C. C. C., Rosa, T. S., Lewis, J. E., Andrade, R. V., & Simões, H. G. (2019). Telomere length and redox balance in master endurance runners: The role of nitric oxide. Experimental Gerontology, 117(0531-5565), 113–118. https://doi.org/10.1016/j.exger.2018.11.018
Telomir Pharmaceuticals, Inc. (2024, November 21). Telomir Pharmaceuticals Confirms Age Reversal, Increased Longevity and Improved Healthspan in Groundbreaking Preclinical Study with Telomir-1. BioSpace. https://www.biospace.com/press-releases/telomir-pharmaceuticals-confirms-age-reversal-increased-longevity-and-improved-healthspan-in-groundbreaking-preclinical-study-with-telomir-1
Vaiserman, A., & Krasnienkov, D. (2021). Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives. Frontiers in Genetics, 11. https://doi.org/10.3389/fgene.2020.630186
Yu, Y., Zhou, L., Yang, Y., & Liu, Y. (2018). Cycloastragenol: An exciting novel candidate for age‑associated diseases (Review). Experimental and Therapeutic Medicine. https://doi.org/10.3892/etm.2018.6501
Zhang, X., Englund, D. A., Aversa, Z., Jachim, S. K., White, T. A., & LeBrasseur, N. K. (2022). Exercise Counters the Age-Related Accumulation of Senescent Cells. Exercise and Sport Sciences Reviews, 50(4), 213–221. https://doi.org/10.1249/JES.0000000000000302
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