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Telomere-based treatment strategy of cardiovascular diseases: imagination comes to reality

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Abstract

The significance of telomere/telomerase biology in the pathogenesis of age-related cardiovascular diseases (CVDs), such as atherosclerosis, hypertension, myocardial infarction (MI), and heart failure, has been increasingly highlighted in recent years. The activation of the DNA damage response (DDR) due to the presence of short telomeres is believed to be a significant upstream signal responsible for inducing a permanent cessation of the cell cycle in cardiomyocytes. Heart failure (HF) is a condition that arises due to the restricted regenerative capacity of the elderly and injured mammalian heart. This limitation may be related to the decreased proliferative potential of cardiac stem cells (CSCs) and cardiomyocytes. The association between CVDs and shorter telomeres provides a foundation for developing therapeutic techniques aimed at elongating telomeres and subsequently restoring the proliferative ability of the adult mammalian heart. This phenomenon offers intriguing prospects for the treatment and prevention of cardiovascular disease (CVD). Further investigation into telomerase gene therapy in the field of cardiac regenerative medicine is justified based on the encouraging outcomes shown in mice models, whereby the reactivation of telomerase in the heart after MI has demonstrated beneficial effects.

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References

  • Aix, E., Gutiérrez-Gutiérrez, Ó., Sánchez-Ferrer, C., Aguado, T., & Flores, I. (2016). Postnatal telomere dysfunction induces cardiomyocyte cell-cycle arrest through P21 activation. Journal of Cell Biology, 213, 571–583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ashrafian, H., Harling, L., Darzi, A., & Athanasiou, T. (2013). Neurodegenerative disease and obesity: What is the role of weight loss and bariatric interventions? Metabolic Brain Disease, 28, 341–353.

    Article  PubMed  Google Scholar 

  • Bär, C., De Jesus, B. B., Serrano, R., Tejera, A., Ayuso, E., Jimenez, V., Formentini, I., Bobadilla, M., Mizrahi, J., De Martino, A., et al. (2014). Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction. Nature Communications, 5, 5863. https://doi.org/10.1038/ncomms6863

    Article  CAS  PubMed  Google Scholar 

  • Bekaert, S., Van Pottelbergh, I., De Meyer, T., Zmierczak, H., Kaufman, J. M., Van Oostveldt, P., & Goemaere, S. (2005). Telomere length versus hormonal and bone mineral status in healthy elderly men. Mechanisms of Ageing and Development, 126, 1115–1122. https://doi.org/10.1016/j.mad.2005.04.007

    Article  CAS  PubMed  Google Scholar 

  • Benetti, R., García-Cao, M., & Blasco, M. A. (2007). Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres. Nature Genetics, 39, 243–250. https://doi.org/10.1038/ng1952

    Article  CAS  PubMed  Google Scholar 

  • Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., De Ferranti, S. D., Floyd, J., Fornage, M., & Gillespie, C. (2017). Heart disease and stroke statistics—2017 update: A Report from the American Heart Association. Circulation, 135, e146–e603.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bergmann, O., Zdunek, S., Felker, A., Salehpour, M., Alkass, K., Bernard, S., Sjostrom, S. L., Szewczykowska, M., Jackowska, T., & Dos Remedios, C. (2015). Dynamics of cell generation and turnover in the human heart. Cell, 161, 1566–1575.

    Article  CAS  PubMed  Google Scholar 

  • Bernardes de Jesus, B., & Blasco, M. A. (2013). Telomerase at the intersection of cancer and aging. Trends in Genetics, 29, 513–520. https://doi.org/10.1016/j.tig.2013.06.007

    Article  CAS  PubMed  Google Scholar 

  • 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, 691–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blackburn, E. H. (2000). Telomere states and cell Fates. Nature, 408, 53–56.

    Article  CAS  PubMed  Google Scholar 

  • Blackburn, E. H. (2001). Switching and signaling at the telomere. Cell, 106, 661–673. https://doi.org/10.1016/S0092-8674(01)00492-5

    Article  CAS  PubMed  Google Scholar 

  • Blackburn, E. H., Epel, E. S., & Lin, J. (1979). Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science, 2015(350), 1193–1198. https://doi.org/10.1126/science.aab3389

    Article  CAS  Google Scholar 

  • Blasco, M. A., Lee, H. W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997). Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell, 91, 25–34. https://doi.org/10.1016/S0092-8674(01)80006-4

    Article  CAS  PubMed  Google Scholar 

  • Bodnar, A. G., Kim, N. W., Effros, R. B., & Chiu, C. P. (1996). Mechanism of telomerase induction during T cell activation. Experimental Cell Research, 228, 58–64. https://doi.org/10.1006/excr.1996.0299

    Article  CAS  PubMed  Google Scholar 

  • 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. (1979). Extension of life-span by introduction of telomerase into normal human cells. Science, 1998(279), 349–352. https://doi.org/10.1126/science.279.5349.349

    Article  Google Scholar 

  • Booth, S. A., & Charchar, F. J. (2017). Cardiac telomere length in heart development, function, and disease. Physiological Genomics, 49, 368–384. https://doi.org/10.1152/physiolgenomics.00024.2017

    Article  CAS  PubMed  Google Scholar 

  • Booth, S. A., Wadley, G. D., Marques, F. Z., Wlodek, M. E., & Charchar, F. J. (2018). Fetal growth restriction shortens cardiac telomere length, but this is attenuated by exercise in early life. Physiological Genomics, 50, 956–963. https://doi.org/10.1152/physiolgenomics.00042.2018

    Article  CAS  PubMed  Google Scholar 

  • Brandt, M., Dörschmann, H., Khraisat, S., Knopp, T., Ringen, J., Kalinovic, S., Garlapati, V., Siemer, S., Molitor, M., & Göbel, S. (2022). Telomere shortening in hypertensive heart disease depends on oxidative DNA damage and predicts impaired recovery of cardiac function in heart failure. Hypertension, 79, 2173–2184.

    Article  CAS  PubMed  Google Scholar 

  • Brouilette, S. W., Moore, J. S., McMahon, A. D., Thompson, J. R., Ford, I., Shepherd, J., Packard, C. J., & Samani, N. J. (2007). Telomere length, risk of coronary heart disease, and statin treatment in the west of scotland primary prevention study: A nested case-control Study. The Lancet, 369, 107–114.

    Article  CAS  Google Scholar 

  • Butt, H. Z., Atturu, G., London, N. J., Sayers, R. D., & Bown, M. J. (2010). Telomere length dynamics in vascular disease: A review. European Journal of Vascular and Endovascular Surgery, 40, 17–26.

    Article  CAS  PubMed  Google Scholar 

  • Calado, R. T., Brudno, J., Mehta, P., Kovacs, J. J., Wu, C., Zago, M. A., Chanock, S. J., Boyer, T. D., & Young, N. S. (2011). Constitutional Telomerase Mutations Are Genetic Risk Factors for Cirrhosis. Hepatology, 53, 1600–1607.

    Article  CAS  PubMed  Google Scholar 

  • Canela, A., Vera, E., Klatt, P., & Blasco, M. A. (2007). High-throughput telomere length quantification by FISH and its application to human population studies. Proceedings of the National Academy of Sciences, 104, 5300–5305.

    Article  CAS  Google Scholar 

  • Cawthon, R. M., Smith, K. R., O’Brien, E., Sivatchenko, A., & Kerber, R. A. (2003). Association between telomere length in blood and mortality in people aged 60 years or older. Lancet, 361, 393–395. https://doi.org/10.1016/S0140-6736(03)12384-7

    Article  CAS  PubMed  Google Scholar 

  • Cesselli, D., Beltrami, A. P., D’Aurizio, F., Marcon, P., Bergamin, N., Toffoletto, B., Pandolfi, M., Puppato, E., Marino, L., & Signore, S. (2011). Effects of age and heart failure on human cardiac stem cell function. American Journal of Pathology, 179, 349–366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021). Telomeres: History, health, and hallmarks of aging. Cell, 184, 306–322. https://doi.org/10.1016/j.cell.2020.12.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chilton, W., O’Brien, B., & Charchar, F. (2017). Telomeres, aging and exercise: Guilty by association? International Journal of Molecular Sciences, 18, 2573.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chimenti, C., Kajstura, J., Torella, D., Urbanek, K., Heleniak, H., Colussi, C., Di Meglio, F., Nadal-Ginard, B., Frustaci, A., & Leri, A. (2003). Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circulation Research, 93, 604–613.

    Article  CAS  PubMed  Google Scholar 

  • Codd, V., Nelson, C. P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J. L., Hottenga, J. J., Fischer, K., Esko, T., & Surakka, I. (2013). Identification of seven loci affecting mean telomere length and their association with disease. Nature Genetics, 45, 422–427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collado, M., Blasco, M. A., & Serrano, M. (2007). Cellular senescence in cancer and aging. Cell, 130, 223–233.

    Article  CAS  PubMed  Google Scholar 

  • D’Mello, M. J. J., Ross, S. A., Briel, M., Anand, S. S., Gerstein, H., & Paré, G. (2015). Association between shortened leukocyte telomere length and cardiometabolic outcomes: Systematic review and meta-analysis. Circulation. Cardiovascular Genetics, 8, 82–90.

    Article  PubMed  Google Scholar 

  • Dagarag, M., Ng, H., Lubong, R., Effros, R. B., & Yang, O. O. (2003). Differential impairment of lytic and cytokine functions in senescent human immunodeficiency virus type 1-specific cytotoxic T lymphocytes. Journal of Virology, 77, 3077–3083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Lange, T. (2002). Protection of mammalian telomeres. Oncogene, 21, 532–540.

    Article  PubMed  Google Scholar 

  • De Lange, T. (2005). Shelterin: The protein complex that shapes and safeguards human telomeres. Genes & Development, 19, 2100–2110. https://doi.org/10.1101/gad.1346005

    Article  CAS  Google Scholar 

  • de Lange, T., Shiue, L., Myers, R. M., Cox, D. R., Naylor, S. L., Killery, A. M., & Varmus, H. E. (1990). Structure and variability of human chromosome ends. Molecular and Cellular Biology, 10, 518–527. https://doi.org/10.1128/mcb.10.2.518-527.1990

    Article  PubMed  PubMed Central  Google Scholar 

  • De Meyer, T., Nawrot, T., Bekaert, S., De Buyzere, M. L., Rietzschel, E. R., & Andrés, V. (2018). Telomere length as cardiovascular aging biomarker: JACC review topic of the week. Journal of the American College of Cardiology, 72, 805–813.

    Article  PubMed  Google Scholar 

  • del López-Armas, G. C., Ramos-Márquez, M. E., Navarro-Meza, M., Macías-Islas, M. Á., Saldaña-Cruz, A. M., Zepeda-Moreno, A., Siller-López, F., & Cruz-Ramos, J. A. (2023). Leukocyte telomere length predicts severe disability in relapsing-remitting multiple sclerosis and correlates with mitochondrial DNA copy number. International Journal of Molecular Sciences, 24, 916.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dimmeler, S., & Leri, A. (2008). Aging and disease as modifiers of efficacy of cell therapy. Circulation Research, 102, 1319–1330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisenberg, D. T. A. (2014). Inconsistent inheritance of telomere length (TL): Is offspring TL more strongly correlated with maternal or paternal TL? European Journal of Human Genetics, 22, 8–9.

    Article  CAS  PubMed  Google Scholar 

  • Eisenberg, D. T. A., Salpea, K. D., Kuzawa, C. W., Hayes, M. G., & Humphries, S. E. (2011). Substantial variation in QPCR measured mean blood telomere lengths in young men from Eleven European Countries. American Journal of Human Biology, 23, 228–231. https://doi.org/10.1002/ajhb.21126

    Article  PubMed  Google Scholar 

  • Engelhardt, M., Ozkaynak, M. F., Drullinsky, P., Sandoval, C., Tugal, O., Jayabose, S., & Moore, M. A. S. (1998). Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy. Leukemia, 12, 13–24.

    Article  CAS  PubMed  Google Scholar 

  • Entringer, S., Epel, E. S., Kumsta, R., Lin, J., Hellhammer, D. H., Blackburn, E. H., Wüst, S., & Wadhwa, P. D. (2011). Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences, 108, E513–E518.

    Article  CAS  Google Scholar 

  • Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences, 101, 17312–17315.

    Article  CAS  Google Scholar 

  • Epel, E. S., Merkin, S. S., Cawthon, R., Blackburn, E. H., Adler, N. E., Pletcher, M. J., & Seeman, T. E. (2009). The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly Men. Aging, 1, 81–88. https://doi.org/10.18632/aging.100007

    Article  CAS  Google Scholar 

  • Farzaneh-Far, R., Lin, J., Epel, E. S., Harris, W. S., Blackburn, E. H., & Whooley, M. A. (2010b). Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA, 303, 250–257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farzaneh-Far, R., Lin, J., Epel, E., Lapham, K., Blackburn, E., & Whooley, M. A. (2010a). Telomere length trajectory and its determinants in persons with coronary artery disease: Longitudinal Findings from the Heart and Soul Study. PLoS ONE, 5, e8612. https://doi.org/10.1371/journal.pone.0008612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrón, S., Mira, H., Franco, S., Cano-Jimenez, M., Bellmunt, E., Ramírez, C., Fariñas, I., & Blasco, M. A. (2004). Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development, 131, 4059–4070. https://doi.org/10.1242/dev.01215

    Article  CAS  PubMed  Google Scholar 

  • Flores, I., Canela, A., Vera, E., Tejera, A., Cotsarelis, G., & Blasco, M. A. (2008). The longest telomeres: A general signature of adult stem cell compartments. Genes & Development, 22, 654–667.

    Article  CAS  Google Scholar 

  • Flores, I., Cayuela, M. L., & Blasco, M. A. (1979). Molecular biology: Effects of telomerase and telomere length on epidermal stem cell behavior. Science, 2005(309), 1253–1256. https://doi.org/10.1126/science.1115025

    Article  Google Scholar 

  • Gardner, M., Bann, D., Wiley, L., Cooper, R., Hardy, R., Nitsch, D., Martin-Ruiz, C., Shiels, P., Sayer, A. A., Barbieri, M., et al. (2014). Gender and telomere length: Systematic review and meta-analysis. Experimental Gerontology, 51, 15–27. https://doi.org/10.1016/j.exger.2013.12.004

    Article  CAS  PubMed  Google Scholar 

  • Griffith, J. D., Comeau, L., Rosenfield, S., Stansel, R. M., Bianchi, A., Moss, H., & De Lange, T. (1999). Mammalian telomeres end in a large duplex loop. Cell, 97, 503–514.

    Article  CAS  PubMed  Google Scholar 

  • Guan, J. Z., Maeda, T., Sugano, M., Oyama, J., Higuchi, Y., & Makino, N. (2007). Change in the telomere length distribution with age in the Japanese population. Molecular and Cellular Biochemistry, 304, 353–360.

    Article  CAS  PubMed  Google Scholar 

  • Haendeler, J., Hoffmann, J., Diehl, J. F., Vasa, M., Spyridopoulos, I., Zeiher, A. M., & Dimmeler, S. (2004). Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells. Circulation Research, 94, 768–775.

    Article  CAS  PubMed  Google Scholar 

  • Hannum, G., Guinney, J., Zhao, L., Zhang, L. I., Hughes, G., Sadda, S., Klotzle, B., Bibikova, M., Fan, J.-B., & Gao, Y. (2013). Genome-wide methylation profiles reveal quantitative views of human aging rates. Molecular Cell, 49, 359–367.

    Article  CAS  PubMed  Google Scholar 

  • Harley, C. B., Futcher, A. B., & Greider, C. W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature, 345, 458–460. https://doi.org/10.1038/345458a0

    Article  CAS  PubMed  Google Scholar 

  • Harris, S. E., Deary, I. J., MacIntyre, A., Lamb, K. J., Radhakrishnan, K., Starr, J. M., Whalley, L. J., & Shiels, P. G. (2006). The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people. Neuroscience Letters, 406, 260–264.

    Article  CAS  PubMed  Google Scholar 

  • Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25, 585–621.

    Article  CAS  PubMed  Google Scholar 

  • Hemmeryckx, B., Hohensinner, P., Swinnen, M., Heggermont, W., Wojta, J., & Lijnen, H. R. (2016). Antioxidant treatment improves cardiac dysfunction in a murine model of premature aging. Journal of Cardiovascular Pharmacology, 68, 374–382.

    Article  CAS  PubMed  Google Scholar 

  • Herrera, E., Samper, E., Martín-Caballero, J., Flores, J. M., Lee, H.-W., & Blasco, M. A. (1999). Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO Journal, 18, 2950–2960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann, J., Erben, Y., Zeiher, A. M., Dimmeler, S., & Spyridopoulos, I. (2009). Telomere length-heterogeneity among myeloid cells is a predictor for chronological ageing. Experimental Gerontology, 44, 363–366. https://doi.org/10.1016/j.exger.2009.02.006

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann, J., Richardson, G., Haendeler, J., Altschmied, J., Andrés, V., & Spyridopoulos, I. (2021). Telomerase as a therapeutic target in cardiovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 41, 1047–1061.

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann, J., & Spyridopoulos, I. (2011). Telomere length in cardiovascular disease: New challenges in measuring this marker of cardiovascular aging. Future Cardiology, 7, 693–707. https://doi.org/10.2217/fca.11.55

    Article  CAS  Google Scholar 

  • Hooijberg, E., Ruizendaal, J. J., Snijders, P. J. F., Kueter, E. W. M., Walboomers, J. M. M., & Spits, H. (2000). Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase. The Journal of Immunology, 165, 4239–4245.

    Article  CAS  PubMed  Google Scholar 

  • Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14, 3156. https://doi.org/10.1186/gb-2013-14-10-r115

    Article  Google Scholar 

  • Iancu, E. M., Speiser, D. E., & Rufer, N. (2008). Assessing ageing of individual T lymphocytes: Mission impossible? Mechanisms of Ageing and Development, 129, 67–78.

    Article  CAS  PubMed  Google Scholar 

  • Jakob, S., Schroeder, P., Lukosz, M., Büchner, N., Spyridopoulos, I., Altschmied, J., & Haendeler, J. (2008). Nuclear protein tyrosine phosphatase Shp-2 is one important negative regulator of nuclear export of telomerase reverse transcriptase. Journal of Biological Chemistry, 283, 33155–33161. https://doi.org/10.1074/jbc.M805138200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang, R., Hauser, E. R., Kwee, L. C., Shah, S. H., Regan, J. A., Huebner, J. L., Kraus, V. B., Kraus, W. E., & Ward-Caviness, C. K. (2022). The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes. Clinical Epigenetics, 14, 165. https://doi.org/10.1186/s13148-022-01380-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin, X., Pan, B., Dang, X., Wu, H., & Xu, D. (2018). Relationship between short telomere length and stroke: A meta-analysis. Medicine 97.

  • Kajstura, J., Gurusamy, N., Ogórek, B., Goichberg, P., Clavo-Rondon, C., Hosoda, T., D’Amario, D., Bardelli, S., Beltrami, A. P., & Cesselli, D. (2010). Myocyte turnover in the aging human heart. Circulation Research, 107, 1374–1386.

    Article  CAS  PubMed  Google Scholar 

  • Kaur, P., Wu, D., Lin, J., Countryman, P., Bradford, K. C., Erie, D. A., Riehn, R., Opresko, P. L., & Wang, H. (2016). Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2. Science and Reports, 6, 20513.

    Article  CAS  Google Scholar 

  • Khincha, P. P., Bertuch, A. A., Agarwal, S., Townsley, D. M., Young, N. S., Keel, S., Shimamura, A., Boulad, F., Simoneau, T., & Justino, H. (2017). Pulmonary arteriovenous malformations: An uncharacterised phenotype of dyskeratosis congenita and related telomere biology disorders. European Respiratory Journal 49.

  • Kovalenko, O. A., Caron, M. J., Ulema, P., Medrano, C., Thomas, A. P., Kimura, M., Bonini, M. G., Herbig, U., & Santos, J. H. (2010). A mutant telomerase defective in nuclear-cytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction. Aging Cell, 9, 203–219. https://doi.org/10.1111/j.1474-9726.2010.00551.x

    Article  CAS  PubMed  Google Scholar 

  • Kuhlow, D., Florian, S., von Figura, G., Weimer, S., Schulz, N., Petzke, K. J., Zarse, K., Pfeiffer, A. F. H., Rudolph, K. L., & Ristow, M. (2010). Telomerase deficiency impairs glucose metabolism and insulin secretion. Aging (albany NY), 2, 650.

    Article  CAS  PubMed  Google Scholar 

  • Lanna, A., Vaz, B., D’Ambra, C., Valvo, S., Vuotto, C., Chiurchiù, V., Devine, O., Sanchez, M., Borsellino, G., Akbar, A. N., et al. (2022). An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory. Nature Cell Biology, 24, 1461–1474. https://doi.org/10.1038/s41556-022-00991-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lansdorp, P. M. (1998). Self-renewal of stem cells. Humana Press.

    Book  Google Scholar 

  • Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998). Essential role of mouse telomerase in highly proliferative organs. Nature, 392, 569–574.

    Article  CAS  PubMed  Google Scholar 

  • Leri, A., Franco, S., Zacheo, A., Barlucchi, L., Chimenti, S., Limana, F., Nadal-Ginard, B., Kajstura, J., Anversa, P., & Blasco, M. A. (2003). Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with P53 upregulation. EMBO Journal, 22, 131–139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindsey, J., McGill, N. I., Lindsey, L. A., Green, D. K., & Cooke, H. J. (1991). In vivo loss of telomeric repeats with age in humans. Mutation Research DNAging, 256, 45–48. https://doi.org/10.1016/0921-8734(91)90032-7

    Article  CAS  Google Scholar 

  • Liu, D., O’Connor, M. S., Qin, J., & Songyang, Z. (2004). Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. Journal of Biological Chemistry, 279, 51338–51342.

    Article  CAS  PubMed  Google Scholar 

  • Liu, L., Bailey, S. M., Okuka, M., Muñoz, P., Li, C., Zhou, L., Wu, C., Czerwiec, E., Sandler, L., & Seyfang, A. (2007). telomere lengthening early in development. Nature Cell Biology, 9, 1436–1441.

    Article  CAS  PubMed  Google Scholar 

  • López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153, 1194–1217.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ludlow, A. T., Witkowski, S., Marshall, M. R., Wang, J., Lima, L. C. J., Guth, L. M., Spangenburg, E. E., & Roth, S. M. (2012). Chronic exercise modifies age-related telomere dynamics in a tissue-specific fashion. Journals of Gerontology-Series A Biological Sciences and Medical Sciences, 67A, 911–926. https://doi.org/10.1093/gerona/gls002

    Article  CAS  Google Scholar 

  • Lynch, S. M., Peek, M. K., Mitra, N., Ravichandran, K., Branas, C., Spangler, E., Zhou, W., Paskett, E. D., Gehlert, S., Degraffinreid, C., et al. (2016). Race, ethnicity, psychosocial factors, and telomere length in a multicenter setting. PLoS ONE, 11, e0146723. https://doi.org/10.1371/journal.pone.0146723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marion, R. M., Strati, K., Li, H., Tejera, A., Schoeftner, S., Ortega, S., Serrano, M., & Blasco, M. A. (2009). Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell, 4, 141–154. https://doi.org/10.1016/j.stem.2008.12.010

    Article  CAS  PubMed  Google Scholar 

  • Marques, F. Z., Booth, S. A., Prestes, P. R., Curl, C. L., Delbridge, L. M. D., Lewandowski, P., Harrap, S. B., & Charchar, F. J. (2016). Telomere dynamics during aging in polygenic left ventricular hypertrophy. Physiological Genomics, 48, 42–49.

    Article  CAS  PubMed  Google Scholar 

  • Martínez, P., & Blasco, M. A. (2011). Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nature Reviews Cancer, 11, 161–176. https://doi.org/10.1038/nrc3025

    Article  CAS  PubMed  Google Scholar 

  • Martínez, P., & Blasco, M. A. (2018). Heart-breaking telomeres. Circulation Research, 123, 787–802.

    Article  PubMed  Google Scholar 

  • Mather, K. A., Jorm, A. F., Milburn, P. J., Tan, X., Easteal, S., & Christensen, H. (2010). No associations between telomere length and age-sensitive indicators of physical function in mid and later life. Journals of Gerontology-Series A Biological Sciences and Medical Sciences, 65A, 792–799. https://doi.org/10.1093/gerona/glq050

    Article  CAS  Google Scholar 

  • Matthews, C., Gorenne, I., Scott, S., Figg, N., Kirkpatrick, P., Ritchie, A., Goddard, M., & Bennett, M. (2006). Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: Effects of telomerase and oxidative stress. Circulation Research, 99, 156–164.

    Article  CAS  PubMed  Google Scholar 

  • McCully, K. S. (2018). Chemical pathology of homocysteine VI. Aging, cellular senescence, and mitochondrial dysfunction. Annals of Clinical Laboratory Science, 48, 677–687.

    CAS  PubMed  Google Scholar 

  • Mollova, M., Bersell, K., Walsh, S., Savla, J., Das, L. T., Park, S.-Y., Silberstein, L. E., Dos Remedios, C. G., Graham, D., & Colan, S. (2013). Cardiomyocyte proliferation contributes to heart growth in young humans. Proceedings of the National Academy of Sciences, 110, 1446–1451.

    Article  CAS  Google Scholar 

  • Mwasongwe, S., Gao, Y., Griswold, M., Wilson, J. G., Aviv, A., Reiner, A. P., & Raffield, L. M. (2017). Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study. Atherosclerosis, 266, 41–47. https://doi.org/10.1016/j.atherosclerosis.2017.09.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakada, Y., Canseco, D. C., Thet, S., Abdisalaam, S., Asaithamby, A., Santos, C. X., Shah, A. M., Zhang, H., Faber, J. E., & Kinter, M. T. (2017). Hypoxia induces heart regeneration in adult mice. Nature, 541, 222–227.

    Article  CAS  PubMed  Google Scholar 

  • Narducci, M. L., Grasselli, A., Biasucci, L. M., Farsetti, A., Mulè, A., Liuzzo, G., La Torre, G., Niccoli, G., Mongiardo, R., & Pontecorvi, A. (2007). High telomerase activity in neutrophils from unstable coronary plaques. Journal of the American College of Cardiology, 50, 2369–2374.

    Article  CAS  PubMed  Google Scholar 

  • Njajou, O. T., Hsueh, W.-C., Blackburn, E. H., Newman, A. B., Wu, S.-H., Li, R., Simonsick, E. M., Harris, T. M., Cummings, S. R., & Cawthon, R. M. (2009). Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. Journals of Gerontology Series a: Biomedical Sciences and Medical Sciences, 64, 860–864.

    Article  Google Scholar 

  • O’Donovan, A., Epel, E., Lin, J., Wolkowitz, O., Cohen, B., Maguen, S., Metzler, T., Lenoci, M., Blackburn, E., & Neylan, T. C. (2011b). Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder. Biological Psychiatry, 70, 465–471. https://doi.org/10.1016/j.biopsych.2011.01.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Donovan, A., Pantell, M. S., Puterman, E., Dhabhar, F. S., Blackburn, E. H., Yaffe, K., Cawthon, R. M., Opresko, P. L., Hsueh, W. C., Satterfield, S., et al. (2011a). Cumulative inflammatory load is associated with short leukocyte telomere length in the health, aging and body composition study. PLoS ONE, 6, e19687. https://doi.org/10.1371/journal.pone.0019687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogami, M., Ikura, Y., Ohsawa, M., Matsuo, T., Kayo, S., Yoshimi, N., Hai, E., Shirai, N., Ehara, S., & Komatsu, R. (2004). Telomere shortening in human coronary artery diseases. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 546–550.

    Article  CAS  PubMed  Google Scholar 

  • Oikawa, S., Tada-Oikawa, S., & Kawanishi, S. (2001). Site-specific DNA damage at the GGG sequence by UVA involves acceleration of telomere shortening. Biochemistry, 40, 4763–4768. https://doi.org/10.1021/bi002721g

    Article  CAS  PubMed  Google Scholar 

  • Okuda, K., Khan, M. Y., Skurnick, J., Kimura, M., Aviv, H., & Aviv, A. (2000). Telomere attrition of the human abdominal aorta: Relationships with age and atherosclerosis. Atherosclerosis, 152, 391–398.

    Article  CAS  PubMed  Google Scholar 

  • Olovnikov, A. M. (1973). A theory of marginotomy: The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. Journal of Theoretical Biology, 41, 181–190.

    Article  CAS  PubMed  Google Scholar 

  • Park, J. I. I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., et al. (2009). telomerase modulates wnt signalling by association with target gene chromatin. Nature, 460, 66–72. https://doi.org/10.1038/nature08137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Passos, J. F., Saretzki, G., & Von Zglinicki, T. (2007). DNA damage in telomeres and mitochondria during cellular senescence: Is there a connection? Nucleic Acids Research, 35, 7505–7513. https://doi.org/10.1093/nar/gkm893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perna, L., Zhang, Y., Mons, U., Holleczek, B., Saum, K.-U., & Brenner, H. (2016). Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clinical Epigenetics, 8, 1–7. https://doi.org/10.1186/s13148-016-0228-z

    Article  Google Scholar 

  • Peters, M. J., Joehanes, R., Pilling, L. C., Schurmann, C., Conneely, K. N., Powell, J., Reinmaa, E., Sutphin, G. L., Zhernakova, A., Schramm, K., et al. (2015). The transcriptional landscape of age in human peripheral blood. Nature Communications, 6, 8570. https://doi.org/10.1038/ncomms9570

    Article  CAS  PubMed  Google Scholar 

  • Petersen, S., Saretzki, G., & von Zglinicki, T. (1998). Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Experimental Cell Research, 239, 152–160.

    Article  CAS  PubMed  Google Scholar 

  • Porrello, E. R., Mahmoud, A. I., Simpson, E., Johnson, B. A., Grinsfelder, D., Canseco, D., Mammen, P. P., Rothermel, B. A., Olson, E. N., & Sadek, H. A. (2013). Regulation of neonatal and adult mammalian heart regeneration by the MiR-15 family. Proceedings of the National Academy of Sciences, 110, 187–192.

    Article  CAS  Google Scholar 

  • Price, L. H., Kao, H.-T., Burgers, D. E., Carpenter, L. L., & Tyrka, A. R. (2013). Telomeres and early-life stress: An overview. Biological Psychiatry, 73, 15–23.

    Article  CAS  PubMed  Google Scholar 

  • Proctor, C. J., & Kirkwood, T. B. L. (2002). Modelling telomere shortening and the role of oxidative stress. Mechanisms of Ageing and Development, 123, 351–363. https://doi.org/10.1016/S0047-6374(01)00380-3

    Article  CAS  PubMed  Google Scholar 

  • Puente, B. N., Kimura, W., Muralidhar, S. A., Moon, J., Amatruda, J. F., Phelps, K. L., Grinsfelder, D., Rothermel, B. A., Chen, R., & Garcia, J. A. (2014). The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell, 157, 565–579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quach, A., Levine, M. E., Tanaka, T., Lu, A. T., Chen, B. H., Ferrucci, L., & Horvath, S. (2018). Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Agro Food Industry Hi-Tech, 29, 20–21.

    Google Scholar 

  • Révész, D., Milaneschi, Y., Verhoeven, J. E., Lin, J., & Penninx, B. W. J. H. (2015). Longitudinal associations between metabolic syndrome components and telomere shortening. Journal of Clinical Endocrinology and Metabolism, 100, 3050–3059. https://doi.org/10.1210/JC.2015-1995

    Article  CAS  PubMed  Google Scholar 

  • Robin, J. D., Ludlow, A. T., Batten, K., Magdinier, F., Stadler, G., Wagner, K. R., Shay, J. W., & Wright, W. E. (2014). Telomere position effect: Regulation of gene expression with progressive telomere shortening over long distances. Genes & Development, 28, 2464–2476.

    Article  Google Scholar 

  • Rufer, N., Brümmendorf, T. H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M., & Lansdorp, P. M. (1999). Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. Journal of Experimental Medicine, 190, 157–168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rufer, N., Migliaccio, M., Antonchuk, J., Humphries, R. K., Roosnek, E., & Lansdorp, P. M. (2001). Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Blood, 98, 597–603. https://doi.org/10.1182/blood.V98.3.597

    Article  CAS  PubMed  Google Scholar 

  • Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., & Walkey, C. (2011). Telomere dysfunction induces metabolic and mitochondrial compromise. Nature, 470, 359–365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samani, N. J., Boultby, R., Butler, R., Thompson, J. R., & Goodall, A. H. (2001). Telomere shortening in atherosclerosis. Lancet, 358, 472–473. https://doi.org/10.1016/S0140-6736(01)05633-1

    Article  CAS  PubMed  Google Scholar 

  • Sandell, L. L., & Zakian, V. A. (1993). Loss of a yeast telomere: Arrest, recovery, and chromosome loss. Cell, 75, 729–739.

    Article  CAS  PubMed  Google Scholar 

  • Sanders, J. L., Cauley, J. A., Boudreau, R. M., Zmuda, J. M., Strotmeyer, E. S., Opresko, P. L., Hsueh, W. C., Cawthon, R. M., Li, R., Harris, T. B., et al. (2009). Leukocyte telomere length is not associated with BMD, osteoporosis, or fracture in older adults: Results from the health, aging and body composition study. Journal of Bone and Mineral Research, 24, 1531–1536. https://doi.org/10.1359/jbmr.090318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanders, J. L., & Newman, A. B. (2013). Telomere length in epidemiology: A biomarker of aging, age-related disease, both, or neither? Epidemiologic Reviews, 35, 112–131. https://doi.org/10.1093/epirev/mxs008

    Article  PubMed  PubMed Central  Google Scholar 

  • Saretzki, G., Murphy, M. P., & Von Zglinicki, T. (2003). MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell, 2, 141–143.

    Article  CAS  PubMed  Google Scholar 

  • Sarin, K. Y., Cheung, P., Gilison, D., Lee, E., Tennen, R. I., Wang, E., Artandi, M. K., Oro, A. E., & Artandi, S. E. (2005). Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature, 436, 1048–1052. https://doi.org/10.1038/nature03836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaetzlein, S., Lucas-Hahn, A., Lemme, E., Kues, W. A., Dorsch, M., Manns, M. P., Niemann, H., & Rudolph, K. L. (2004). Telomere length is reset during early mammalian embryogenesis. Proceedings of the National Academy of Sciences, 101, 8034–8038.

    Article  CAS  Google Scholar 

  • Scheller Madrid, A., Rode, L., Nordestgaard, B. G., & Bojesen, S. E. (2016). Short Telomere Length and Ischemic Heart Disease: Observational and Genetic Studies in 290 022 Individuals. Clinical Chemistry, 62, 1140–1149.

    Article  PubMed  Google Scholar 

  • Shahidi, N. T., & Diamond, L. K. (1961). Testosterone-induced remission in aplastic anemia of both acquired and congenital types: Further observations in 24 cases. New England Journal of Medicine, 264, 953–967.

    Article  CAS  PubMed  Google Scholar 

  • Shammas, M. A. (2011). Telomeres, lifestyle, cancer, and aging. Current Opinion in Clinical Nutrition and Metabolic Care, 14, 28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharifi-Sanjani, M., Oyster, N. M., Tichy, E. D., Bedi, K. C., Jr., Harel, O., Margulies, K. B., & Mourkioti, F. (2017). Cardiomyocyte-specific telomere shortening is a distinct signature of heart failure in humans. Journal of the American Heart Association, 6, e005086.

    Article  PubMed  PubMed Central  Google Scholar 

  • Smith, J. A., Raisky, J., Ratliff, S. M., Liu, J., Kardia, S. L. R., Turner, S. T., Mosley, T. H., & Zhao, W. (2019). Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older african americans. BMC Medical Genomics, 12, 141. https://doi.org/10.1186/s12920-019-0585-5

    Article  PubMed  PubMed Central  Google Scholar 

  • Stadler, G., Rahimov, F., King, O. D., Chen, J. C. J., Robin, J. D., Wagner, K. R., Shay, J. W., Emerson, C. P., Jr., & Wright, W. E. (2013). Telomere position effect regulates DUX4 in human facioscapulohumeral muscular dystrophy. Nature Structural & Molecular Biology, 20, 671–678.

    Article  CAS  Google Scholar 

  • Starkweather, A. R., Alhaeeri, A. A., Montpetit, A., Brumelle, J., Filler, K., Montpetit, M., Mohanraj, L., Lyon, D. E., & Jackson-Cook, C. K. (2014). An integrative review of factors associated with telomere length and implications for biobehavioral research. Nursing Research, 63, 36–50. https://doi.org/10.1097/NNR.0000000000000009

    Article  PubMed  PubMed Central  Google Scholar 

  • Stefler, D., Malyutina, S., Maximov, V., Orlov, P., Ivanoschuk, D., Nikitin, Y., Gafarov, V., Ryabikov, A., Voevoda, M., Bobak, M., et al. (2018). Leukocyte telomere length and risk of coronary heart disease and stroke mortality: Prospective evidence from a Russian Cohort. Science and Reports, 8, 16627. https://doi.org/10.1038/s41598-018-35122-y

    Article  CAS  Google Scholar 

  • Strandberg, T. E., Saijonmaa, O., Tilvis, R. S., Pitkälä, K. H., Strandberg, A. Y., Miettinen, T. A., & Fyhrquist, F. (2011b). Association of telomere length in older men with mortality and midlife body mass index and smoking. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 66A, 815–820. https://doi.org/10.1093/gerona/glr064

    Article  CAS  Google Scholar 

  • Strandberg, T. E., Saijonmaa, O., Tilvis, R. S., Pitkälä, K. H., Strandberg, A. Y., Salomaa, V., Miettinen, T. A., & Fyhrquist, F. (2011a). Telomere length in old age and cholesterol across the life course. Journal of the American Geriatrics Society, 59, 1979–1981. https://doi.org/10.1111/j.1532-5415.2011.03610_13.x

    Article  PubMed  Google Scholar 

  • Svačina, Š. (2020). Obesity and cardiovascular disease. Vnitrni Lekarstvi, 66, 89–91. https://doi.org/10.1161/01.atv.0000216787.85457.f3

    Article  PubMed  Google Scholar 

  • Tang, N. L. S., Woo, J., Suen, E. W. C., Liao, C. D., Leung, J. C. S., & Leung, P. C. (2010). The effect of telomere length, a marker of biological aging, on bone mineral density in elderly population. Osteoporosis International, 21, 89–97.

    Article  CAS  PubMed  Google Scholar 

  • Terai, M., Izumiyama-Shimomura, N., Aida, J., Ishikawa, N., Sawabe, M., Arai, T., Fujiwara, M., Ishii, A., Nakamura, K., & Takubo, K. (2013). Association of telomere shortening in myocardium with heart weight gain and cause of death. Science and Reports, 3, 2401.

    Article  Google Scholar 

  • Uygur, A., & Lee, R. T. (2016). Mechanisms of cardiac regeneration. Developmental Cell, 36, 362–374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valdes, A. M., Andrew, T., Gardner, J. P., Kimura, M., Oelsner, E., Cherkas, L. F., Aviv, A., & Spector, T. D. (2005). Obesity, cigarette smoking, and telomere length in women. Lancet, 366, 662–664. https://doi.org/10.1016/S0140-6736(05)66630-5

    Article  CAS  PubMed  Google Scholar 

  • Valdes, A. M., Richards, J. B., Gardner, J. P., Swaminathan, R., Kimura, M., Xiaobin, L., Aviv, A., & Spector, T. D. (2007). Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis. Osteoporosis International, 18, 1203–1210. https://doi.org/10.1007/s00198-007-0357-5

    Article  CAS  PubMed  Google Scholar 

  • Valenzuela, H. F., & Effros, R. B. (2002). Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus. Clinical Immunology, 105, 117–125. https://doi.org/10.1006/clim.2002.5271

    Article  CAS  PubMed  Google Scholar 

  • van der Harst, P., van der Steege, G., de Boer, R. A., Voors, A. A., Hall, A. S., Mulder, M. J., van Gilst, W. H., & van Veldhuisen, D. J. (2007). Telomere length of circulating leukocytes is decreased in patients with chronic heart failure. Journal of the American College of Cardiology, 49, 1459–1464. https://doi.org/10.1016/j.jacc.2007.01.027

    Article  CAS  PubMed  Google Scholar 

  • Vera, E., Canela, A., Fraga, M. F., Esteller, M., & Blasco, M. A. (2008). Epigenetic regulation of telomeres in human cancer. Oncogene, 27, 6817–6833. https://doi.org/10.1038/onc.2008.289

    Article  CAS  PubMed  Google Scholar 

  • Verde, Z., Reinoso-Barbero, L., Chicharro, L., Garatachea, N., Resano, P., Sánchez-Hernández, I., Rodríguez González-Moro, J. M., Bandrés, F., Santiago, C., & Gómez-Gallego, F. (2015). Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length. Environmental Research, 140, 488–494. https://doi.org/10.1016/j.envres.2015.05.008

    Article  CAS  PubMed  Google Scholar 

  • Verhulst, S., Dalgård, C., Labat, C., Kark, J. D., Kimura, M., Christensen, K., Toupance, S., Aviv, A., Kyvik, K. O., & Benetos, A. (2016). A short leucocyte telomere length is associated with development of insulin resistance. Diabetologia, 59, 1258–1265.

    Article  CAS  PubMed  Google Scholar 

  • Von Zglinicki, T. (2002). Oxidative stress shortens telomeres. Trends in Biochemical Sciences, 27, 339–344.

    Article  Google Scholar 

  • Von Zglinicki, T., Pilger, R., & Sitte, N. (2000). Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radical Biology & Medicine, 28, 64–74. https://doi.org/10.1016/S0891-5849(99)00207-5

    Article  Google Scholar 

  • Waring, C. D., Vicinanza, C., Papalamprou, A., Smith, A. J., Purushothaman, S., Goldspink, D. F., Nadal-Ginard, B., Torella, D., & Ellison, G. M. (2014). The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. European Heart Journal, 35, 2722–2731.

    Article  CAS  PubMed  Google Scholar 

  • Weischer, M., Bojesen, S. E., & Nordestgaard, B. G. (2014). Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart. PLoS Genetics, 10, e1004191.

    Article  PubMed  PubMed Central  Google Scholar 

  • Weng, N. (2008). Telomere and adaptive immunity. Mechanisms of Ageing and Development, 129, 60–66. https://doi.org/10.1016/j.mad.2007.11.005

    Article  CAS  PubMed  Google Scholar 

  • Weng, N.-P., Levine, B. L., June, C. H., & Hodes, R. J. (1996). Regulated expression of telomerase activity in human T lymphocyte development and activation. Journal of Experimental Medicine, 183, 2471–2479.

    Article  CAS  PubMed  Google Scholar 

  • Werner, C., Fürster, T., Widmann, T., Pöss, J., Roggia, C., Hanhoun, M., Scharhag, J., Büchner, N., Meyer, T., & Kindermann, W. (2009). Physical exercise prevents cellular senescence in circulating leukocytes and in the vessel wall. Circulation, 120, 2438–2447.

    Article  PubMed  Google Scholar 

  • Wong, J. Y. Y., De Vivo, I., Lin, X., Fang, S. C., & Christiani, D. C. (2014). The relationship between inflammatory biomarkers and telomere length in an occupational prospective cohort study. PLoS ONE, 9, e87348. https://doi.org/10.1371/journal.pone.0087348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong, L., Yang, G., Guo, T., Zeng, Z., Liao, T., Li, Y., Li, Y., Chen, F., Yang, S., Kang, L., et al. (2023). 17-Year follow-up of association between telomere length and all-cause mortality, cardiovascular mortality in individuals with metabolic syndrome: Results from the NHANES Database Prospective Cohort Study. Diabetology and Metabolic Syndrome, 15, 247. https://doi.org/10.1186/s13098-023-01206-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, C., Wang, Z., Su, X., Da, M., Yang, Z., Duan, W., & Mo, X. (2020). Association between leucocyte telomere length and cardiovascular disease in a large general population in the United States. Science and Reports, 10, 80. https://doi.org/10.1038/s41598-019-57050-1

    Article  CAS  Google Scholar 

  • Zaragoza, C., Gomez-Guerrero, C., Martin-Ventura, J. L., Blanco-Colio, L., Lavin, B., Mallavia, B., Tarin, C., Mas, S., Ortiz, A., & Egido, J. (2011). Animal models of cardiovascular diseases. Biomedicine Research International, 2011, 1–13.

    Google Scholar 

  • Zglinicki, Tv., & Martin-Ruiz, C. M. (2005). Telomeres as biomarkers for ageing and age-related diseases. Current Molecular Medicine, 5, 197–203.

    Article  Google Scholar 

  • Zhang, K., Ma, Y., Luo, Y., Song, Y., Xiong, G., Ma, Y., Sun, X., & Kan, C. (2023). Metabolic diseases and healthy aging: Identifying environmental and behavioral risk factors and promoting public health. Frontiers in Public Health. https://doi.org/10.3389/fpubh.2023.1253506

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou, H., Liu, S., Zhang, N., Fang, K., Zong, J., An, Y., & Chang, X. (2022). Downregulation of Sirt6 by CD38 Promotes Cell Senescence and Aging. Aging (albany NY), 14, 9730.

    CAS  PubMed  Google Scholar 

  • Zurek, M., Altschmied, J., Kohlgrüber, S., Ale-Agha, N., & Haendeler, J. (2016). Role of telomerase in the cardiovascular system. Genes (basel), 7, 29. https://doi.org/10.3390/genes7060029

    Article  CAS  PubMed  Google Scholar 

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  1. Biochemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62521, Egypt

    Mohammed Abdel-Gabbar & Mohamed G. M. Kordy

  2. Nanophotonics and Applications (NPA) Lab, Physics Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt

    Mohamed G. M. Kordy

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The authors affirm their contribution to the work in the following manner: The study's concept and design were conducted by MA-G, while MA-G was responsible for data collecting. The analysis and interpretation of findings were carried out by both MA-G and MGMK. The first draft of the paper was prepared by MA-G and MGMK. The findings were evaluated by all authors and the final version of the paper was approved.

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Abdel-Gabbar, M., Kordy, M.G.M. Telomere-based treatment strategy of cardiovascular diseases: imagination comes to reality. GENOME INSTAB. DIS. 5, 61–75 (2024). https://doi.org/10.1007/s42764-024-00123-x

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