EVOLUTION HELPED US IN MANY WAYS, FIGHTING AGING IS NOT ONE OF THEM

Aging is an inevitable and irreversible process, and it is difficult to define precisely.

17 min readSep 5, 2022

On August 4, 1997, Jeanne Louise Calment — a French woman died peacefully in a nursing home in Arles, aged 122 years and 164 days. At the time, she was recognized as having the highest attested age in history, more than anyone who has ever lived [1]. Jeanne witnessed the construction of the Eiffel Tower, met Vincent van Gogh in person when he entered her father’s workshop, and lived a quiet life for an unprecedented length of time. Jeanne remained healthy both physically and mentally for most of her life, even fencing at the age of 85, cycling at the age of 100, and appearing in a film about van Gogh — “Vincent et moi” at the age of 114, as herself [2].

Not many of us can do that, most live and die between the ages of 70 and 90 on average, which is already the ideal limit. The development of science and technology helps to improve the quality of life, prolongs the average life of people, but also leads to an unpredictable consequence, meaning living longer with diseases. The human body is designed to be born and grow old over the years, spend most of our ending days in a hospital or nursing home, then most of us die in beds, in pain or in peace (if you have lived a healthy life and are lucky enough). This is actually sad for anyone. Most of us don’t expect to grow old in sickness and then die a tormented death. Obviously, aging lowers life quality, with a long process of forcing us to witness our memory fading, our body weakening day by day. If aging is so inefficient and makes death inevitable, then why has over the course of 3.5 billion years humans evolved from single-celled organisms to the life form at the top of the food chain as it is today, life doesn’t evolve in a way that helps us fight aging?

1. An inevitable fact that cannot be reversed

Aging — “senescence” can be derived from the Latin word “senex” — meaning old age, which is a process that occurs throughout the adult life of any living organism [3]. Biologically, senescence is the process by which cells mature, age, and permanently stop dividing but cannot die. Over time, a large number of old cells will accumulate in tissues throughout the body that are still functioning, and can release toxic agents that cause damage to nearby cells, playing a role in the development of cancer and other incurable diseases. The old age of a living organism is often accompanied by signs of decline in biological functions, the ability to adapt to stress, and an increased risk of disease. Thus, death is the inevitable end of aging, and getting older means spending more time fighting against disease.

In the past, maximum lifespan (the biological maximum limit of life under ideal conditions) was thought to be immutable, subject to the aging process, which is considered unadaptable or dependent on genetic traits. In 1912, the experiments of culturing cells from chicken hearts by Nobel laureate Dr. Alexis Carrel created a new dogma in the scientific world that accepted immortality as an intrinsic property of all cells. Specifically, in an optimal environment, the cells of higher organisms (like us) can divide continuously, leading to the existence of immortality [4]. However, in the 1960s, Leonard Hayflick — a young scientist active in the field of cancer completely rejected Carrel’s view of cell immortality when determining the maximum number of divisions that human cells can undergo during cultivation. Accordingly, Hayflick determined that chicken cells divide at least 30 times before death, while the connective tissue of a normal person will divide about 50 times until it stops completely. This limit puts the maximum human lifespan at about 115 years, and is known as the Hayflick limit [5]. For people in industrialized countries life expectancy has increased significantly during the 20th century, with average life expectancy increasing from 30 to 45 years at the beginning of the century to around 67 years by the end of the century thanks to improvements on health care, nutrition and quality of life. At the turn of the 21st century, demographic projections suggest that life expectancy for those who maintain a healthy lifestyle will continue to increase to about 100 years or more. The remarkable increase in life expectancy over the past two or three centuries is arguably the great collective achievement of mankind, when previously life expectancy was initially only about 25 years [6].

Aging is an inevitable and irreversible process, and it is difficult to define precisely. A widely accepted descriptive idea defines aging as the part of the life cycle, when a person is born and goes through childhood, adolescence, adulthood and then begins to age at a certain point. The aging process does not start at the same time in everyone, nor does all organs in the same person age at the same rate, but it inevitably happens to anyone and in any organ. From a biological point of view, our organs start to shut down such as bones stop growing and degenerate, tissues don’t regenerate as quickly as before, hormone secretion decreases (like a drop in testosterone in men or menopause in women). Basically, aging is not a disease but a fact of life, and it facilitates the emergence of cancer, heart failure, kidney failure, dementia… There are many different theories about aging, each of which will explain one or more problems of this aging process. And so far there is no single theory that can explain all aspects of aging, and the theories themselves often contradict or even cancel each other out. Modern biological theories of aging in humans can now be divided into major categories such as programmed theory, damage theory, genetic theory and evolutionary theory [7], in addition to several other theories of psychology and biochemistry.

The theory of programmed aging holds that humans are designed to age and that our cells have a predetermined lifespan limit, encoded in the body. These include:

- Gene theory: Sees aging as the result of sequentially “turning on” and “turning off” certain genes, with lifespan defined as the time it takes for defects to manifest.

- Endocrine theory: Changing the rhythm of the body’s biological clock through the action of hormones to control the rate of aging.

- Immune Theory: Says that the immune system is programmed to decline over time, increasing vulnerability to aging and death.

Meanwhile, Damage Theory (or error theory) is opposite to the programmed theory that aging is caused by cellular changes that occur randomly and completely without planned, causing inevitable problems like the entropy dimension, including:

- Theory of wear and tear: The theory that our cells and tissues wear out leading to aging. Like machines, they simply wear out. However, animals have the ability to repair themselves, so this theory does not fit the data of biological systems.

- Survival rate theory: The higher the metabolic rate of an organism, the shorter its lifespan.

- Free-radical theory: Due to the oxidative-stress imbalance that accumulates with age, it leads to instability and high reactivity between cells, causing them to malfunction and damage the expression mechanism.

- Genome instability theory: According to this theory, aging occurs because the body gradually loses the ability to repair DNA damage.

Another theory supports the idea that our lifespan is regulated by genes we get from our parents, meaning aging is largely based on genetics (like eye color). This genetic theory is reinforced by the fact that people with long-lived parents or grandparents tend to have longer life expectancies, or identical twins will have more similar lifespan than siblings. The genetic theory of aging focuses on telomeres, which are repetitive pieces of DNA that protect the ends of chromosomes as they multiply. Over time, telomeres become shorter and thus make biochemical processes more prone to malfunction, and induce aging.

And finally there is the Evolutionary Theory of Aging, which is based on the basic concept of natural selection that deals with adaptive features of organisms, and aging is based on natural selection. It assumes that an organism begins to age after it has reached its reproductive peak and has passed on adaptive traits to the next generation. Accordingly, this theory holds that humans possess beneficial genes that help to survive, develop and maintain the species by reproduction. However, these types of genetic mutations will come back to attack us, creating a disadvantage for the rest of our lives. This theory specifically includes:

- The theory of mutation accumulation: First proposed by Peter Medawar in 1952, it is assumed that harmful mutations will accumulate due to genetic drift by the weakening of natural selection, from which they manifest in later generations, leading to the evolution of these harmful mutations — called senescence.

- Contradictory Effect Theory: George Williams in 1957, following what Medawar initiated, hypothesized that a gene mutation can lead to both good and bad traits, while promoting fertility but it also has negative effects later on.

- Somatic mutation theory: Thomas Kirkwood (1977) states that the more metabolic sources geared towards reproduction, the less focused on DNA repair, leading to cell damage and post-reproductive aging.

The evolutionary theory of aging will also be mentioned below to make it clearer why evolution doesn’t help us get rid of aging but clearly shows its inefficiencies in life. Besides, invoking many theories about aging hopefully does not make the reader feel overwhelmed, because it only aims to show the fact that because aging occurs in so many aspects that science in general and Gerontology in particular have been really thorough with the study of aging. Because any benefit to be derived from these studies is to bring people one step closer to the pursuit of the highest quality of life without having to experience the decline of old age, or even immortality. But why are we still growing old and dying, or why has evolution chosen to keep aging for humans (as well as for nearly all other living things)?

2. The challenge of evolution and its reward, aging

Essentially, the evolutionary goal of any species will be the continuity of that species’ genetic material into the future. And this can be done by extending the lifespan of individual organisms so that they live long enough, thereby maximizing reproduction leading to the next generation. More specifically, according to the logic of natural selection, which is also the key mechanism of evolution, in any population, the alleles (variations in the genotype) of the individual that produce the most progeny will increase in frequency in successive generations, replacing alleles that are less successful [8]. And to be successful in producing descendants, the individual must also be able to successfully survive, and live long enough to reach reproductive age. From there, natural selection eventually produced individuals that were properly designed to survive and reproduce in their environment.

However, if survival and reproduction have always been preceded by natural selection, why is aging in living organisms so universal? The second law of thermodynamics states that the natural tendency of any isolated system is to gradually increase disorder and degrade to a more disordered state [9]. The aging process in this respect is similar in that it brings death as the inevitable final outcome, but so there exists a paradox between the optimal dynamics of evolution in organisms and the inevitable deterioration, is aging. Why doesn’t evolution create a biological template for organisms in which aging never occurs? Explaining aging through an evolutionary perspective was pioneered by three scientists Peter Medawar (1952), George Williams (1957) and Thomas Kirkwood (1977), making the main point that aging influenced by the key mechanisms of evolution are natural selection, mutation/genetic variation. They also make the important conjecture that immortality — or at least an indefinite lifespan — is unlikely to be the end result of evolution by natural selection.

Specifically, in 1952, British biologist Peter Medawar proposed the first evolutionary theory of aging, and called it the theory of mutation accumulation [10]. As he conducted the research, he noted uncanny similarities between aging and Huntington’s disease — an inherited disease that causes damage to nerve cells in the brain that often leads to death. Starting from asking the question, if this is a genetic disease and always fatal, why doesn’t natural selection remove the alleles responsible for causing the disease from our genes? The answer has to do with the fact that Huntington’s disease often occurs late, during or even after the reproductive period. Based on the basic concept of evolution, an allele that harms the health but does not affect the reproductive success of the individual carrying it will generally be immune to the liquidation of natural selection. In other words, natural selection will “blindly” ignore late-onset mutations. Self-revealing mutations later in life cannot be reverse-selected, if reproduction has taken place and passed on to the next generation. In contrast, a mutated allele that compromises early fertility would be strongly opposed by natural selection. According to this logic, early active mutations will manifest themselves during the period of reproductive activity, so they will soon be eliminated by natural selection if it harms the survival and reproduction of the organism. Since then, Medawar has been keenly aware that the same logic can be applied to the aging process. As new mutations in the genome continue to occur, he argues, and cause more harm than good, any harmful mutations with the potential to affect reproduction or survival but only present in late life stages are not subject to natural selection, and can accumulate in the genome over generations. By the time the mutations burst into the causative agents of disease, by which time the individual has passed the reproductive age, it will be seen as a process of body degradation, or aging — has been “approved” by evolution.

The theory of mutation accumulation was completed in 1957 by the American evolutionary biologist, George Williams, after he realized that there was still something hidden in the theory that Medawar had only mentioned briefly, and introduced the theory of Medawar to a higher level. In particular, Williams further explained the correlation between an early-acting and late-onset mutation, which he called the Contradictory Effect Theory [11] when it suggested that if a gene mutation carries both good and bad traits, but the good side outweighs the bad, then natural selection will “favor” it to pass on, and this mutation will not be eliminated. He showed that when an allele has a beneficial effect on survival or reproduction in the early stages (when selection is still strong), but causes a disadvantage later on (when the intensity of selection gets weaker) then these alleles will be positively favored by natural selection and will enrich these alleles, even though they can wreak havoc on things later. The positive effect of an allele that acts early compared to the negative effect of late onset is known as antagonistic omnidirectional, or opposing effect. One corollary of this theory is that mutations that slow aging or even prolong life often have adverse effects on survival or early fertility will also be removed. This opposing effect model presents aging as an inappropriate by-product of selection for survival and reproduction in early life. In other words, we can carry many mutations that are beneficial for survival, development and maintenance of the race when young, but in return, aging is inevitable. For example, the mutation that causes Huntington’s disease can improve fertility and reduce the risk of cancer [12], or the mutation that causes sickle cell disease is thought to increase resistance to malaria [ 13].

In 1977, British biologist Thomas Kirkwood supplemented his vision of evolution affecting aging with the Somatic Mutation Theory when it proposed that evolution had emerged in the trade-off between reproduction and survival. [14]. He argues that in an environment with limited resources, each individual must choose between survival or reproduction, specifically as more resources are poured into reproduction, less is left for survivability. This concept is practically observed in the natural environment, when species have to spend a variety of expenses in an effort to find suitable breeding objects, such as:

- Searching costs: Expanding the scope of observation and search will increase the ability to select suitable breeding objects, but it will be at the expense of time and physical strength, as well as the risk of being hunted.

- Cost of pregnancy: Pregnancy and child raising are very costly in terms of energy, at this time, daily activities or outbreaks of danger will easily cause physical injury, or even affect the ability to forage or hunt for food.

- Disease risk: Interaction with other individuals increases the risk of contact-borne infectious disease, which reduces immunity, which leads to a trade-off in longevity.

- Risk of mating: Females are at greater risk of abuse than males, or vice versa (such as female mantises that eat their partners immediately after mating [15]).

Because reproduction is at the heart of evolution and is meant to sustain the race at the species level, more investment in reproduction means less investment in body maintenance and repair body at the DNA level, which leads to cell damage, shortens telomeres, accumulates harmful alleles, damages stem cells and causes aging. If the investment is too low in survivability, or in self-repair, there will be no evolutionary benefit as organisms may die before reproductive age. And conversely, too much investment in survival also leads to less ability to find suitable breeding objects. However, the Somatic Mutation Theory is still limited by not suggesting any specific cellular mechanism by which an organism can transfer energy to repair the body through reproduction, but merely stating perspective on why aging can be caused by reproduction. Unlike the two theories of mutation accumulation and opposing effects, which clearly establish the trade-offs of evolution through growth and aging, Soma mutation theory is still controversial in many certain aspects outside the field of evolutionary biology [16].

3. Because evolution has made everyone grow old, and die

Collectively, all three theories looking at aging from an evolutionary point of view contribute to the fact that humans are among the creatures with the longest post-reproductive lifespan, continuing for almost a third of the entire lifespan. It was initially thought that reproductive survival was out of evolutionary control, due to the often high rates of mortality outside the environment due to predators, infectious diseases, and accidents in human evolutionary history. So from the very beginning, humans never developed the maintenance or repair mechanisms that would allow the body to regenerate after reproduction because most individuals die very early, so continuing to survive after reproduction has no use since the task of passing on genetic material has been completed. However, this statement was later superseded by the emergence of the opposite effect theory. Therefore in fact, aging is manifested more and more clearly because we are getting older thanks to the development of medicine or the quality of life, so we care about it. This adds to the explanation that evolution has chosen to prioritize reproduction and allows beneficial mutations to occur first, and aging comes later as an inevitable if humans can live long enough. On the other hand, the fact that humans continue to survive after the reproductive stage also presents a selective advantage as the presence of older individuals (postpartum women) can increase the likelihood of successful childbirth for the children in the third generation.

For more than thousands of years, human survival has largely depended on resistance to infectious diseases, so genetic adaptations leading to inflammatory responses have taken precedence. The inflammatory response is part of a biological response system that responds to harmful stimuli, fights infection from lesions, and helps the host survive to reproductive age. But after reaching reproductive age, these inflammatory responses also contribute to the development of chronic degenerative diseases, where it is clear that the mechanism of natural selection favors beneficial mutations in the early period, but the organism must pay the price later.

More specifically, human survival relies heavily on resistance to infectious diseases, and natural selection sets us apart from other mammals — through how humans constantly create new ways of life. First, we eliminate the danger of cold by the ability to create fire about 400,000 years ago [17]. Additional contributions to reducing the likelihood of cold deaths from the creation of clothing, the transition of hunter-gatherer lifestyles to agrarian civilization in the Neolithic, or the construction of houses. Developed agriculture also helps to create a stable food supply, reducing the likelihood that individuals will starve and die from starvation. At the same time, intelligence superior to other species has helped humans use tools and weapons, have the ability to communicate and cooperate in groups, helping to reduce the number of people who die when hunting or being attacked by wild animals. As a result of eliminating key threats such as cold, food, and isolation, selective pressure on combating infectious diseases has increased. Thus, the ability to resist infectious diseases becomes an important criterion of natural selection, increasing the predominance of resistance to infection to be able to survive to reproductive age, which means that humans will invest in the ability to maintain their fitness.

Evidence of genetic adaptation against infection is the innate immune system (the inflammatory response), the first and sufficient line of defense against most invading pathogens. In ancient human habitats, not many individuals were able to survive to 30 or 50 years old, and so it is no coincidence that this is the right age for breeding. At this time, harmful mutations that affect after the age of 40 or 50 years will not be selected for resistance because most individuals do not have much post-reproductive lifespan. In other words, late-life chronic or degenerative diseases are in fact causality from natural selection that favors the emergence of beneficial genetic mutations early in life. The selection of an early protective inflammatory response signal will be the trigger for what is known as age-related, or degenerative, diseases — which are often atherosclerosis, heart failure, arthritis, hypothyroidism, osteoporosis and diabetes. It is almost conceivable that chronic degenerative diseases of old age — or aging — are a part of our history, shaped by evolution in favor of the survival of the species. It is quite ironic that the more people improve the environment and improve the quality of life, the worse the adverse effects of late age become, manifesting more in each year of increasing life expectancy.

The late writer JRR Tolkien in the Lord of the Rings fantasy he created mentioned about the Human race that, unlike the Elves who were endowed with Immortality, the gift that God Anu gave to Humans, is mortality. With this gift, people have more free will and also know how to make decisions in their short lives. Mentally, I love this gift.

Hmm… but immortality is kinda worth considering.

___________

References:

EVOLUTION HELPED US IN MANY WAYS, FIGHTING AGING IS NOT ONE OF THEM

Aging is an inevitable and irreversible process, and it is difficult to define precisely.

Written by Monster Box