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Brittany Avin McKelvey
Many of us are enticed by the possibility of extending our lives, towards the goal of one day being able to live forever. This wish may be closer to becoming reality with the promise of some research in which the activation of only one enzyme, usually turned off in our cells, could be reactivated to help us live longer. Many companies and scientists have considered activation of the enzyme telomerase to extend years of our life. One big problem with this potential solution? Over 90% of cancers also reactivate telomerase to grow uncontrollably.
Why do we need telomerase?
Our bodies are made up of trillions of cells, and just like us, they are mortal. Our cells cannot continually renew themselves or keep dividing indefinitely, and they eventually reach a limit in their lifespan known as the “Hayflick limit”. Every time a cell divides, the cell loses a small part of its DNA on the end of its chromosomes. To protect the cell from losing valuable DNA, protective caps made of repetitive pieces of DNA, called telomeres, are at the end of the chromosomes. As the cell ages, and goes through divisions, the telomeres continue to shorten. If cells do not have these telomeres, the cell loses important information on its chromosomes that can have disastrous effects. At the Hayflick limit, the telomeres have been continually shortened through cell divisions until they are too short to protect the cell’s DNA, and this alerts the cell to stop dividing, or risk damage to its genes.
How could telomerase help extend lifespan?
Telomerase is the enzyme in cells that adds DNA sequence to telomeres. Telomerase, however, is not activated in normal cells in our body. Therefore in normal cells, after a finite number of divisions, the cells stop dividing. Cells that stop dividing and growing are associated with aging– including illness, weakness, and organ failure, as cells that are not dividing cannot restore damaged tissue. The shortening telomeres can increase the morbidity of other diseases or stressors on the body. The idea of telomerase activation for extended lifespan then is that telomerase could add DNA to telomeres so the time a cell has to continue to divide and live increases. Telomerase activation would be an anti-aging agent, as cells could live longer and repair tissue to help humans as a whole live longer. Already, some monetization has occurred for companies touting products to increase telomeres to live longer. There are supplements touted to “stop time” by decreasing telomere shortening, and others to test your telomere length to determine your relative age (there is no proof showing a direct causation of telomere length and lifespan, and there is a large range of normal telomere lengths in the population). Products currently on the market are neither FDA approved nor shown to be valid in any capacity. And even if telomerase were activated in normal cells as a therapeutic, there may only be a small amount of increase in lifespan. But even if there is a slight increase, wouldn’t a little be better than nothing? Most scientists say no because of large evidence in the field: activating telomerase and extending telomere length can cause cancer.
Telomerase activation in cancer
While telomerase is not activated in normal cells, it is turned back on in approximately 90% of cancer cells. Activating telomerase in cancer cells results in immortalizing the cancer cells, reversing telomere shortening and allowing the cancer cells to continue their rapid division, one of the hallmarks of cancer. Increasing telomerase activity in mice has shown to increase the risk for cancer development. So the idea of increasing telomerase activity to lengthen telomeres for increased lifespan may also increase the risk of developing cancer. The limited capacity cells have to divide is a good thing, because as cells divide, they make mistakes in replicating their genome. Those mistakes, or mutations, can cause cancer. By having a limit to the times a cell can divide, it is a mechanism to protect the cells from becoming cancerous. By activating telomerase, these cells have the ability to continue to divide indefinitely, further picking up potentially harmful mutations, in what can lead to cancer. In cancer treatment, actually inhibiting telomerase, stopping it from lengthening telomeres, has been a goal for decades to stop cells from dividing uncontrollably. There are currently multiple cancer drugs for inhibiting telomerase, including drugs targeting the activity of telomerase and immunotherapy targeting telomerase. Cancer cells in culture experiments show a decrease in invasion when treated with these inhibitors. There are direct telomerase inhibitors that prohibit binding of the enzyme on the telomeres as well.
Overall, there is a fine balance between cell growth and death. Too much of either can be detrimental. But as humans try to explore mechanisms for increasing lifespan, we have to be careful about wanting our cells to divide forever. Increasing telomerase could allow old cells that have stopped growing, and stopped being able to repair, to then be able to keep dividing to repair and stop or reverse aging. But uncontrolled division of cells, by turning on telomerase, is exactly what cancer cells employ to continue on their destructive path. As future therapies and drugs continue to be developed, developing an ability to finely control telomerase expression in cells to help, and not hurt, is needed, while telomerase will continue to be explored as an anti-cancer therapeutic.
Edited by Rachel Cherney
Eissenberg, J. Telomeres, Cancer & Aging: Live Long & Prosper?. Mo Med 110(1): 10–16. (2013) PMID: 30323466.
Photograph used from Pixabay, without modification.