Why Do We Age?
Cells have the entire blueprint of the host organism as DNA. Human bodies are composed of these cells that continuously regenerate themselves. Each cell deteriorates over time or are destroyed by external factors such as wounds, but will eventually be replenished by cellular division. It is said that after 7~10 years all cells are completely replaced in a human body. If our cells can regenerate damaged parts, why do we age or die? 9 factors that are said to contribute to aging are known as the “Hallmarks of Aging”. But, not much about aging is still certain and is still under extensive research.
Hallmarks of Aging
1. Epigenetic Alterations
Epigenetics is the change in DNA expression without changing the sequence or coding of the DNA. It is easy to understand epigenetics as a system of locks and keys that are locked or unlocked depending on certain external stimuli. These epigenetic alterations are caused by DNA methylation in which methyl groups are added to the DNA molecule or histone modification in which a part of the DNA coils around a histone protein, making it unreadable. As an example, height growth is controlled by these epigenetics and is turned off once the person has reached maturity. As you age, these epigenetics are mistakenly/accidentally turned on or off and the accumulation of these damages cause diseases and malfunctions in the body. Because much of these epigenetics are controlled by external stimuli, some of the epigenetics can be controlled by diets, medicine, and other lifestyle elements.
▲ Structure of DNA [10]
2. Loss of Proteostasis
▲ Prions in Creutzfeldt-Jakob disease [11]
Proteins are extremely important in the structure of the human body; not only that proteins regulate much of the chemical reactions necessary for our survival. The cell’s main job is to make these proteins, but as people age, damages accumulate. These damages can cause proteins to misfold and lose their intended function and can even become a prion. A prion is a misfolded protein that causes other normally folded proteins to misfold in the same way. There are examples such as a Mad cow disease in cows and Creutzfeldt-Jakob disease in humans. In both cases, the prions slowly destroy the brain and spinal cords. Another example is Alzheimer’s disease which is also caused by misfolded proteins.
3. Deregulated Nutrient Sensing
Calcium signaling, mitochondrial dysfunction, ER stress, oxidative stress damage cells which are caused by metabolism and its byproducts. The cells send messages to the hypothalamus, but these damages can disrupt these messages to signal for greater food intake when the body doesn’t need it. This could potentially cause other problems such as obesity.
4. Mitochondrial Dysfunction
Mitochondria being the powerhouse of the cell produces most of the body’s energy, but also creates the most free radicals. Free radicals are strong oxidizing agents that pull off electrons from most molecules they encounter. For a complex system such as the human body, that is not favorable. It is said that for anti-aging procedures, the right amount of mitochondrial dysfunction is necessary because the free radicals that this process creates triggers the cells to regenerate themselves which then actually become beneficial.
5. Cellular Senescence
Unlike Amoebas and Hydras that can duplicate forever, the cells in human bodies eventually degenerate. This is caused by telomere attrition (will be explained later) or other forms of damage to a cell. After complete degeneration to the point that further cellular division is not possible, the cell becomes a senescent cell that doesn’t die but secretes damaging molecules. These senescent cells undergo apoptosis (self-destruction) or are destroyed by the immune system, and it is only a problem when they linger for too long. It was seen in mice that the removal of these senescent cells increased lifespan, and there seems to be a correlation.
▲ Cellular Senescence [1]
6. Stem Cell Exhaustion
Stem cells are important for the regeneration and repair of virtually every tissue and organ. As the body ages, the number of stem cells and the stem cell’s ability to divide when necessary decreases. Its susceptibility to cancer also increases. Eventually, the body will not be able to keep up with the repairing of damaged tissues and they will begin to show on the human body as gray hair or wrinkled skin.
7. Altered Intercellular Communication
The brain communicates with other organs like the liver via hormones, and this happens between neighboring cells as well. With age this ability becomes impaired. In addition, in old human bodies, there is a phenomenon called “inflammaging” (inflammation and aging combined) in which the body develops a low-grade chronic systemic inflammation. This inflammation is not healed and remains. There is strong evidence that the main cause of this continuous inflammation is the senescent cells, but it isn’t certain. This low-level inflammation impairs the proper functioning of the immune system and could cause cytokine storms as seen with elderly people who have contracted the COVID-19 Virus.
8. Genomic Instability
From one estimate, it is said that the DNA in each of our cells are attacked and damaged up to 1 million times a day. Fortunately, the body has a system that repairs almost all of this damage. This system is not perfect, however, and the damage accumulates and turns into things like cancer. These errors also become mutations that eventually change the gene pool of the species.
9. Telomere Attrition
During DNA replication, short pieces of DNA are lost at the tips of the chromosomes. To prevent important information from being lost in the process, the cell has a protective cap called a telomere that protects the important parts from being lost. The telomere has the same structure as DNA, but the coding sequences there mean nothing and are gibberish. When telomeres become too short for the cell to divide again, the cell halts its ability to duplicate and becomes a senescent cell.
▲ Telomere Attrition from Repetitive Duplication [8]
Summing it Up
These are not mutually exclusive and are mostly interdependent. One problem could cause another and that could also cause another. The human body can be thought of as a car. A relatively new car could be fixed with easy repairs. A tire exchange here and there and maybe an oil change. But as years go by, gas mileage will worsen, weird sounds could be heard and the engine could stop. Irreversible damage will come one day and the car will become metal scrap. In thinking about death, it is important to observe from the perspective of nature. It is not favorable for an organism beyond fertile age to continue living and consume resources. In addition, these deaths are necessary for the gene pool to become more adept to their environments since the lingering of old genotypes will lessen the probability of a favorable mutation spreading. It is quite possible that it was in nature’s design to make organisms imperfect to be able to evolve.
[1] Austad Steven. 2020. “What are the Hallmarks of Aging?” american federation for Aging Research. https://www.afar.org/what-are-the-hallmarks-of-aging. 08/18/20.
[2] Zant Gary, Liang Ying. 2012. “Concise Review: Hematopoietic Stem Cell Aging, Life Span, and Transplantation”. PubMed Central. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659734/#:~:text=Stem%20cells%20are%20key%20to,immortal%20and%20exempt%20from%20aging.. 08/18/20.
[3] Barras Colin. 2015. “The animals and plants that can live forever”. BBC. http://www.bbc.com/earth/story/20150622-can-anything-live-forever. 08/18/20.
[4] Swanson Charlotte. 2016. “Born to Die: Why Do Humans Get Old?”. ScienceWorld. https://www.scienceworld.ca/stories/born-die-why-do-humans-get-old/. 08/18/20.
[5] López-Otín Carlos, Blasco Maria , Partridge Linda, Serrano Manuel, Kroemer Guido. 2013. “The Hallmarks of Aging”. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/. 08/18/20.
[6] 2017. “Why Age? Should We End Aging Forever?”. Kurzgesagt. https://www.youtube.com/watch?v=GoJsr4IwCm4. 08/18/20.
[7] Menesini Monica. 2016. “Why do our bodies age?”. https://www.youtube.com/watch?v=GASaqPv0t0g. 08/18/20.
[8] Berzin Robin. 2020. “Want to Slow Down Aging? Meet your Telomeres.”. Parsley Health. https://www.parsleyhealth.com/blog/telomeres-stay-young-aging/. 10/04/20.
[9] Hill Steve. 2017. “What is Aging?” Lifespan.io. https://www.lifespan.io/news/aging/. 10/04/20.
[10] “Epigenetics: Fundamentals”. WhatisEpigenetics. https://www.whatisepigenetics.com/fundamentals/. 10/04/20.
[11] “Creutzfeldt-Jakob disease” Mayoclinic. https://www.mayoclinic.org/diseases-conditions/creutzfeldt-jakob-disease/symptoms-causes/syc-20371226. 10/04/20.
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