Eternal Youth: A tale of Reverse Aging by Telomerase

Arka Acharyya, Ramakrishna Mission Vivekananda Centenary College, Rahara

Turning Fantasy into Reality

As we grow older, we experience an increasing number of major life changes, and staying healthy and feeling our best is important at any age. But what if you were 90 years old and one fine morning you surprisingly find yourself back to your 19 years old self in all its glory! Well, science might just have succeeded in making such an impossibility into a reality. We often imagine ourselves wanting to relive days from our youth or childhood, but bathing in this fountain of youth is nothing more than just fantasy. Well, not anymore!

Pioneering research in the field of biosciences has finally turned a mere fantasy into stark reality, as ‘Reverse aging’, or the ability to not just stop the natural process of aging but also restore youth is now possible.

Major advances in science can now slow down the process of cellular senescence with the help of ‘TELOMERASE’, a ribonucleoprotein enzyme. This enzyme has two essential components: 

1. The functional RNA component (called telomerase RNA, or TER), which works as a template for telomeric DNA synthesis; 
2. Another is a catalytic protein– telomerase reverse transcriptase (TERT), having reverse transcriptase activity; solving the end replication problem of eukaryotes. 

In this context, the telomeric DNA sequence, or ‘telomere’ is the terminating end portions of eukaryotic chromosomes, made up of repetitive sequences of non-coding DNA that protects the chromosome from damage. After the discovery of telomerase in the 1980s, it came to be regarded as the ‘Fountain of youth’. 

The Science behind Senescence 

There have been numerous myths and rumors when it comes to the topic of aging and death. But those were soon debunked in 1961 when Leonard Hayflick and Paul Moorhead found the cause of aging at the cellular level. According to their study, a normal human cell population can divide a finite number of times, then they stop the division and enter cellular senescence. This phenomenon is known as ‘Hayflick’s Limit’. Cellular senescence correlates with the length of the telomere. Researchers found that, in human cells, telomeres shorten by 30–200 base pairs per cell division. Cells cannot divide once telomeres shorten to a critical length. Thus, cellular aging appears to correlate with the overall physical aging of an organism. 

Increasing Telomerase causes Malignancy   

Overexpression of telomerase in normal cells is a common feature of cancer. Excessive amounts of telomerase biosynthesis increase the length of telomeres as compared to normal cases. This encourages the growth of malignant tumors. In such a situation, telomerase would be the cause of malignancy.

Overcoming the Barrier

According to Peter M. Lansdorp, who is a cancer geneticist at the University of British Columbia, and Ronald DePinho, another cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston,  protecting telomerase does not only help in preventing aging but also helps in reversing it. According to their study, when mice were engineered to lack telomerase completely, their telomeres progressively shortened over several generations. Causing aging to occur much faster than normal. They were becoming infertile and suffered from age-related conditions, such as diabetes, osteoporosis, and neural degeneration. Even some of them started to die young. DePinho’s team observed that telomerase was switched back by feeding a chemical called 4-OHT. Affected mice could now grow back to normal and they even regained their fertility. Other organs, such as the liver, spleen, and intestines, also recovered from their degenerated states.

Other researchers also claimed that Telomerase based therapy, or more specifically TERT-based gene therapy late in life significantly extends lifespan without recruiting cancer. From these studies, it can be expected that shortly telomerase may be a remarkable solution to premature aging and also be a key to prolonged youth.

Future perspective of Reverse-Aging

Progeria, most appropriately known as Hutchinson-Gilford Progeria Syndrome (HGPS) is an autosomal disorder that was also featured in an Indian film “Paa”. This disease is caused due to a de novo mutation in the LMNA gene, resulting in telomere dysfunction and a premature entry into cellular senescence. Reactivation of telomerase via cell therapy is now being considered as a potential treatment for Progeria. Moreover, restoring telomerase activity could also be a key solution to Werner syndrome fibroblasts (WS). Telomerase is expected to evolve as a promising strategy to combat aging. 

Also read: The Secret of Keeping a Healthy Body and Mind

SOURCE:

1. 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
2. Callaway, E. (2010). Telomerase reverses ageing process. Nature, news.2010.635. https://doi.org/10.1038/news.2010.635
3. Decker, M. L., Chavez, E., Vulto, I., & Lansdorp, P. M. (2009). Telomere length in hutchinson-gilford progeria syndrome. Mechanisms of Ageing and Development, 130(6), 377–383. https://doi.org/10.1016/j.mad.2009.03.001
4. Wyllie, F. S., Jones, C. J., Skinner, J. W., Haughton, M. F., Wallis, C., Wynford-Thomas, D., Faragher, R. G. A., & Kipling, D. (2000). Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts. Nature Genetics, 24(1), 16–17 https://doi.org/10.1038/71630.

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