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Imagine this scenario: You are 90 years old, with gray hair and wrinkled skin. You always carry around a walking cane everywhere you go because the slightest movements from sitting down on a chair to brushing your teeth in the morning cause you tremendous pain in your joints, muscles, and bones. But what if you were able to solve all these problems with a simple shot to the arm, and immediately, all your pain was gone. All your tissues have been rejuvenated. And you have now added 50 to 60 additional years to your lifespan. Wouldn’t that be great? But to do that, we must first solve our problem with senescence.
Senescence, the state in which a cell ceases to divide but is resistant to dying, is commonly associated with aging. It is responsible for the wrinkles on our skin, the gray hair on our head, and other effects of aging. Additionally, the accumulation of senescent cells in our body induces chronic inflammation, interferes with organ function, and can evoke other cells to become senescent. But how do cells become senescent?
Senescence, which is inevitable for almost every cell in our body, can occur when a cell hits the maximum number of cell divisions or incurs DNA damage. DNA damage may arise from inflammation, radiation, chemical hazards, or a number of other methods, and is associated with the development of cancer through the activation of oncogenes, or genes associated with cancer. However, one of the most common ways for senescence to be elicited is by telomere loss, a part of natural aging. Now, one way to imagine this is by looking at the shoelaces on your shoe. The shoelace is the chromosome, which stores genetic information. The plastic cap at the end of the shoelace is the telomere, and every time the cell divides, that plastic cap gets shorter and shorter until it is too short for any more cell replication. When the plastic caps disappear, the shoelaces, representing the chromosomes, simply fray, leading to DNA damage that could induce cellular senescence. Thus, the human cells in our body do not continually replicate forever; in fact, the Hayflick limit theory states that cells can only divide around 40 to 70 times before they enter cell cycle arrest and stop dividing. Hence, as people get older, more and more cells reach that endpoint of cell replication, resulting in more and more senescent cells and, therefore, wrinkles on our skin.
Because of the immense impact of senescence on our health, thousands of scientists around the world are attempting to identify biomarkers for senescent cells. Since if there is a clear marker to separate senescent cells from healthy, dividing cells, then senolytic drugs can be developed to destroy or kill off only the senescent cells in our body. Additionally, inducing senescence in cancer cells could mitigate the detrimental effects they have on the human body. As stated above, telomere shortening, UV radiation, carcinogens such as tobacco or radon, and nearly anything that induces DNA damage can elicit the cell to enter senescence. However, this DNA damage can produce specific gene mutations that cause normal cells to undergo transformation into cancer cells with problematic abnormal cell growth, causing them to constantly divide and neglect any signals that warn them to stop dividing. Hence, senescence, which is permanent cell cycle arrest, could prospectively be induced and halt this uncontrollable cell growth prominent in cancer cells.
However, there are flaws in this way of thinking. First, there is a huge controversy between whether or not there are truly biomarkers for senescence. There are many claims of identifiable markers of specific proteins for senescence; however, many of these claims are diminished by the fact that these proteins have also been found on non-senescent cells (Liu et al., 2018). Thus, these claimed biomarkers are unreliable and not totally indicative of the presence of cellular senescence. In addition, completely eliminating senescent cells can have adverse effects on the human body, as they are involved in wound healing, tumor suppression, and other advantageous benefits for our body despite the drawbacks of aging. Lastly, the risk of cancer increases with age, so even if we could prolong life by inducing senescence, we would still be at risk of developing cancer later on in our life due to inevitable DNA damage.
However, once biomarkers for senescence have been identified, the field of oncology, medicine, and our overall knowledge of the human body would enter a new, revolutionary chapter. Preventing the accumulation of senescent cells in organs and tissues would possibly inhibit signs of aging and prolong lifespans. For example, previous experiments with mice showed that upon being given senolytic drugs, the elimination of senescent cells not only improved physical functioning but also increased their lifespan by approximately 36 percent, indicating that it is only a matter of time before humans are able to find our own ways to lengthen our lifetime.
Edited by Sara Musetti
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