Anti-Aging Strategies Through Telomerase Reactivation

Written By Guest User

5/18/2024

Written By: Dena Mohammadian

During an era in which many feats considered impossible are being conquered through science, there is a high interest in developing drugs/biologics that promote anti-aging. There are many methods in which this can be made possible with one such approach promoting the activation of telomerase. 


Figure 1. Illustration of telomere shortening as cells divide over time. (Whole Health Insider, 2012).



Aging occurs as a result of telomere shortening, an impact of an imperfect DNA replication process. Telomeres are repetitive DNA sequences located at the ends of chromosomes that serve as protective caps to maintain genomic stability [1, 5]. They protect the inner sequence of DNA during DNA replication by preventing the loss of essential genetic information [9]. However, with each replication cycle, telomeres gradually shorten, eventually reaching a critical length that triggers cellular senescence, a key hallmark of aging. Telomerase is an enzyme responsible for counteracting the natural shortening of telomeres that occurs with each cell division [10]. This enzyme complex comprises the Telomerase Reverse Transcriptase (TERT) and the Telomerase RNA (TR) component [10]. Telomerase activity is crucial for maintaining telomere length and cellular longevity. As individuals age, telomeres gradually shorten, leading to cellular senescence, impaired tissue regeneration, and increased susceptibility to age-related diseases. Therefore, strategies to reactivate telomerase and preserve telomere length have garnered significant interest as potential anti-aging interventions.



Several approaches have been explored to target telomerase activity and promote telomere reactivation. One such strategy involves the use of TA-65, a compound derived from the Chinese herb Astragalus membranaceus, which has been shown to activate telomerase and extend telomeres [6]. In a study conducted by Dimitris Tsoukalas in 2019, TA-65 and similar compounds were found to have anti-aging potential, improving glucose tolerance, osteoporosis, and skin fitness in mice [11]. While these studies focused on telomere lengthening and the associated benefits, further research is needed to investigate whether TA-65 can allow cells to surpass the Hayflick Limit and continue replicating indefinitely. Furthermore, sex hormones, such as androgens and estrogens, have been implicated in regulating TERT gene expression and telomerase activity, suggesting a potential role in anti-aging interventions [8].



In recent years, the market for anti-aging products targeting telomerase reactivation has expanded significantly. TA-65 supplements, claiming to promote telomere elongation and cellular rejuvenation, have gained popularity among consumers seeking anti-aging solutions. Despite promising results in preclinical studies, concerns remain regarding the safety and efficacy of TA-65 in humans, particularly about its potential to induce cancerous cell proliferation [9]. While telomerase can stimulate anti-aging properties, it can also stimulate tumorigenesis (the formation of a tumor in the body) when overexpressed [2-4]. Nevertheless, continued research and clinical trials are underway to evaluate the long-term effects of TA-65 and similar compounds on human health and longevity. TERT transcription activators and hormone-based therapies have also emerged as promising approaches to modulate telomerase activity and combat age-related cellular decline [4]. Further research is needed to validate the efficacy and safety of these interventions in clinical settings.



The future of anti-aging strategies through telomere reactivation holds promising avenues for research and development. Advancements in understanding the molecular mechanisms underlying telomerase regulation and telomere maintenance will pave the way for the development of novel therapeutic interventions. Targeted approaches to enhance telomerase activity, such as gene therapy and small molecule drugs, offer potential avenues for personalized anti-aging treatments.


Citations:



  1. Blasco, M. (2007). Telomere length, stem cells and aging. Nat Chem Biol 3, 640–649. https://www.nature.com/articles/nchembio.2007.38

  2. Pereira, B., Ferreira, M. G. (2013). Sowing the seeds of cancer: telomeres and age-associated tumorigenesis. Current Opinion in Oncology 25(1):p 93-98. https://journals.lww.com/co-oncology/fulltext/2013/01000/sowing_the_seeds_of_cancer__telomeres_and.16.aspx

  3. Wang, S., Madu, C.O., Lu, Y. (2019). Telomere and Its Role in Diseases. Oncomedicine, 4, 1-9. https://www.oncm.org/v04p0001.htm

  4. Tenchov, R., Sasso, J. M., Wang, X., Zhou, Q. A. (2024). Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise. ACS Chemical Neuroscience, 15(3), 408-446. https://pubs.acs.org/doi/full/10.1021/acschemneuro.3c00532

  5. Blackburn, E. H., Epel, E.S. (2012). Telomeres and adversity: Too toxic to ignore. Nature, 490(7419), 169-171.. https://pubmed.ncbi.nlm.nih.gov/23060172/

  6. Bernardes de Jesus, 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), 604-21.. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627294/

  7. Cong, Y. S., Wright, W. E., Shay, J. W. (2002). Human telomerase and its regulation. Microbiol Mol Biol Rev., 66(3), 407-25. https://pubmed.ncbi.nlm.nih.gov/12208997/

  8. Calado, R. T., Yewdell, W. T., Wilkerson, K. L., Regal, J. A., Kajigaya, S., Stratakis, C. A., Young, N. S. (2009). Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood, 114 (11), 2236–2243. https://ashpublications.org/blood/article/114/11/2236/25821/Sex-hormones-acting-on-the-TERT-gene-increase

  9. Dahse, R., Fiedler, W., Ernst, G. (1977). Telomeres and telomerase: biological and clinical importance. Clinical Chemistry, 43(5), 708-714. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=7ef34035135f4ba3d41875166898382fc11856b0

  10. Shay, J.W., Wright, W.E. (2019). Telomeres and telomerase: three decades of progress. Nat Rev Genet 20, 299–309. https://www.nature.com/articles/s41576-019-0099-1

  11. Tsoukalas, D., Fragkiadaki, P., Docea, A. O., Alegakis, A. K., Sarandi, E., Thanasoula, M., Spandidos, D. A., Tsatsakis, A., Razgonova, M. P., Calina, D. (2019). Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives. Mol Med Rep, 20(4), 3701-3708. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755196/

  12. Whole Health Insider. (2012). A genetic solution to slowing aging and preventing disease. Retrieved:http://www.wholehealthinsider.com/newsletter/2012/a-genetic-solution-to-slowing-aging-and-preventing-disease/

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