The impact of age, of course, is not limited to organisms. You drive a brand new car off the lot, and ideally it’s in perfect working condition. But by the time it reaches the 100,000 mile mark, the car doesn’t run quite
like it used to. Or, that lovely walking path you discovered when you first moved into your home has now become weathered, the weeds are overgrown, and some of the asphalt has buckled.
Like the car and the walking path, over time your DNA accumulates damage. That’s normal. Our DNA suffers millions of damaging events each day. Fortunately, our cells have powerful mechanisms to repair damage and, by and large, these mechanisms remain active and functional through old age. However, over time, some damage will fail to be repaired and will stay in our DNA. Scientists think this damage and a decrease in the body’s ability to fix itself may be an important component of aging. Most DNA damage is harmless for example, small errors in DNA code, called mutations, are harmless. Other types of DNA damage, for example, when a DNA strand breaks, can have more serious ramifications. Fixing a break in a DNA strand is a complex operation and it is more likely the body will make mistakes when attempting this repair mistakes that could shorten lifespan.
Another kind of DNA damage build-up occurs when a cell divides and passes its genetic information on to its two daughter cells. During cell division, the telomere, a stretch of DNA at each end of a chromosome that doesn’t encode any proteins but instead protects the protein-encoding part of the DNA, becomes shorter.
When the telomere becomes too short, it can no longer protect the cell’s DNA, leaving the cell at risk for serious damage. In most cells, telomere length cannot be restored. Extreme telomere shortening triggers an SOS response, and the cell will do one of three things: stop replicating by turning itself off, becoming what is known as senescent; stop replicating by dying, called apoptosis; or continue to divide, becoming abnormal and potentially dangerous.
Scientists are interested in senescent cells because, although they are turned off, they still work on many levels. For instance, they continue to interact with other cells by both sending and receiving signals. However, senescent cells are different from their earlier selves. They cannot die, and they release molecules that lead to an increased risk for diseases, particularly cancer.
The relationship among cell senescence, cancer, and aging is an area of ongoing investigation. When we are young, cell senescence may be critical in helping to suppress cancer. Senescence makes the cell stop replicating when its telomeres become too short, or when the cell cannot repair other damage to its DNA. Thus, senescence prevents severely damaged cells from producing abnormal and perhaps cancerous daughter cells. However, later in life, cell senescence may actually raise the risk of cancer by releasing certain molecules that make the cells more vulnerable to abnormal function.
Consider fibroblasts, cells that divide about 60 times before turning off. Normally, fibroblasts hold skin and other tissues together via an underlying structure, a scaffold outside the cell, called the extracellular matrix. The extracellular matrix also helps to control the growth of other cells. When fibroblasts turn off, they emit molecules that can change the extracellular matrix and cause inflammation. This disturbs the tissue’s function and contributes to aging. At the same time, the breakdown of the extracellular matrix may contribute to increased risk of cancer with age.
Learning why on a biological level cell senescence goes from being beneficial early in life to having Detrimental effects later in life may reveal some important clues about aging.
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