Jeanne Calment holds the title of the longest lifespan. She was born in France and lived to the age of 122 years and 164 days (1875–1997). The average life expectancy of a human can change according to their country of residence; for most developed countries, it's currently 79 years, so Jeanne Calment’s record must be near impossible to beat, right? Not exactly. In fact, scientists believe that the first person who will biologically be able to live to be 150 years, has already been born (1)! Over the past 40 plus years, the life expectancy of the average human being has drastically improved, going from 67 years for the average American in 1975 to 79 years in 2020 (2).
There can be many reasons for a person's death and the rate at which their ageing affects them, from exercise to diet and even other external factors such as accidents. However, disregarding any and all external and environmental factors, no matter what, all humans are destined to die at some point or another. After all, each cell in our body has a lifespan, so you could say we are programmed to die at some point.
But how is it that we die? What is it that makes our body grow weaker and weaker until we finally kick the bucket? As the years pass, our bodies accumulate genetic damage in the form of DNA lesions. DNA lesions, which are sections of a DNA molecule containing a primary damaged site, can occur naturally when the body's DNA replicates. This explanation is known as the Hayflick Theory, which is also the primary reason why we grow weaker when we enter old age. Nondividing cell organelles called mitochondria are especially prone to damage from DNA lesions. Mitochondria are known as the powerhouse of the cell as they produce adenosine triphosphate or ATP, an organic compound that is the main source of energy for all cellular processes. Mitochondria control a wide range of cell exercises and assume an essential part in programmed cell death; if mitochondrial functions decline, it causes cells and eventually entire organs to deteriorate too.
Other reasons for degeneration due to old age include your genetics. Your genes carry all kinds of genetic information, some of which might be silenced at a young age, and only expressed prominently when you grow older, leading to the development of degenerative diseases, such as Alzheimer’s, which accelerate ageing. Such changes to the pattern of gene expression are known as epigenetic alterations. These can affect the body's tissues and cells.
Even if we could avoid all these harmful DNA genetic alterations and degenerative diseases, not even our natural process for growth, simple DNA replication, could save us. The point at which a cell stops replicating is called cellular senescence. This point for humans is around 50 times, once this is reached, the cell gradually begins to lose its function and dies. But this process becomes a lot more vivid as we age, halting cell growth and cutting short their ability to replicate. Why does this happen? Why can’t our cells just keep dividing?
Well, every cell goes through cell division and replication; mitosis and meiosis are how we grow. Each time a cell divides, it makes a copy of its DNA as well. This DNA is packaged into structures called chromosomes, of which humans have 23 pairs. However, the problem is that this process of DNA replication is not perfect, as it skips over the end of each chromosome while duplicating. To shield against any important DNA info from being cut out, we have telomeres at the end of each chromosome, which are essentially unimportant copies of DNA that we can afford to lose. So every time the cells divide, these telomeres get shorter and shorter as they are skipped over in the process of replication until they are completely used up, and at this point, the cell is unable to divide further.
Fun fact: the inability for never-ending cell replication is what helps us to control cancer, which is essentially the uncontrollable cell division leading to the formation of a tumor (3). Genes that normally block cell cycle progression are known as tumor suppressors. Tumor suppressors prevent the formation of cancerous tumors when they are working correctly.
The concept that helps to illustrate the mechanisms behind cellular ageing, The Hayflick Limit proposed by Leonard Hayflick, states that a typical human cell can duplicate itself just forty to sixty times before it loses the ability, due to the absence of telomeres, to do so anymore. Beyond this, the cell will break down by programmed cell death or apoptosis (4). The slowing down of cell growth, and eventual cell death, present themselves in a variety of ways. For example, in the form of hair loss and grey hair (a reduction in the production of melanin in the hair follicles).
Ageing also affects stem cells that reside in many tissues and have the ability to divide without limits in order to replenish other cells (such as muscle cells, brain cells, damaged tissue, etc). As we get older, stem cells decrease in number and are prone to lose their regenerative potential, affecting tissue renewal and the upkeep of the organ’s original functions.
Other changes revolve around the cells ability to function properly; as they age, cells stop being able to do quality control on proteins, causing the accumulation of damaged and potentially toxic nutrients leading to excessive metabolic activity that could be fatal. Intercellular communication also slows, ultimately undermining the body's functional ability (5).
We have seen all the main biological reasons for ageing, but what about preventing them? Science has come a long way, can't we just stop dying? Or even if not attaining immortality, surely there must be a way to artificially extend our life clocks, like reverse ageing. Now that's a topic for another article.
Written by Nirmal Thomas
1. Statista. (2021, February 3). Life expectancy in the United States, 1860–2020. https://www.statista.com/statistics/1040079/life-expectancy-united-states-all-time/
2. AsapSCIENCE. (2013, March 7). The Science of Aging. YouTube. https://www.youtube.com/watch?v=BkcXbx5rSzw
3. Zane Bartlett. (2014, November 14). The Hayflick Limit | The Embryo Project Encyclopedia. The Embryo Project Encyclopedia. https://embryo.asu.edu/pages/hayflick-limit
4. TED-Ed. (2016, June 9). Why do our bodies age? - Monica Menesini. YouTube. https://www.youtube.com/watch?v=GASaqPv0t0g&t=106s
5. Edermaniger, L. (2020, September 1). Age Reversal Technology Facts And Myths: Can Science Stop Aging? Atlas Biomed Blog | Take Control of Your Health with No-Nonsense News on Lifestyle, Gut Microbes and Genetics. https://atlasbiomed.com/blog/can-science-stop-aging-the-facts-on-age-reversal-technology/
6. Swanson, C. S. (2020, July 13). Born to Die: Why do Humans Get Old? ScienceWorld. https://www.scienceworld.ca/stories/born-die-why-do-humans-get-old/
7. Hewings-Martin, Y. (2017, August 2). Telomeres: What causes biological ageing?MedicalNewsToday.https://www.medicalnewstoday.com/articles/318764
8. Life Noggin. (2015, January 26). WHY DO WE DIE? YouTube. https://www.youtube.com/watch?v=NJbxZoWY_4M
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