Over the past few decades, scientists have proposed several theories to explain the process of aging. As our understanding of biology and related fields has grown, we have abandoned or modified some of these theories to fit our current knowledge. However, some of these outdated theories still hold significant influence on the general public and fuel a multi-billion dollar industry. In this article, I will explore some of these outdated theories, in some cases highlighting what is still relevant, what is inaccurate, and how they have evolved. In a future article, I will delve into the current theories of aging, known as the “Hallmarks of Aging.”
Outdated theories of aging
Among the outdated theories of aging there are:
- Free radical theory of aging
- Wear and tear theory of aging
- Programmed aging theory
- Error accumulation/catastrophe theory of aging
- Neuroendocrine theory of aging
- Immunological theory of aging
- Cross-linking theory of aging
- Rate of living theory of aging
- Hayflick limit theory of aging
- Telomere shortening theory of aging.
- Disposable soma theory of aging
It’s worth noting that in the longevity medicine field we’ve evolved from trying to pinpoint the single reason why we age, like the free radical theory of aging, to investigating the multiple causes and factors that ultimately result in aging. For help with the technical jargon used in this article, please check out the glossary.
Free radical theory of aging
The free radical theory of aging was developed by Professor Harman in the 1950s, at a time when the role of free radicals in human bodies was not yet understood, and the knowledge and tools available were limited. This theory proposed that cells produce metabolites, and some of these byproducts are toxic free radicals. Although we have antioxidant defenses to fight the free radicals, some can pass our defenses and damage proteins, DNA, and organelles within cells, such as the mitochondria.
Twenty years later, the focus shifted to the mitochondria, where 90% of free radicals are produced within a cell, and the damage to its structure and mitochondrial DNA. Although free radicals do cause damage, such as DNA damage, lipid peroxidation, protein oxidation, and cell membrane damage, researchers found no benefits when investigating antioxidant supplementation in various models. In fact, some instances of antioxidant supplementation not only failed to prevent disease or delay death, but actually led to cancer or premature death. In other experiments, researchers tried to increase free radical damage and DNA mutations, but this failed to result in accelerated aging.
In the 21st century, we are finally understanding that free radicals are not just a damaging molecule, but they are fundamental for cell signaling purposes and are part of the cell immune response against infection, as well as for triggering regenerative processes or modulating blood flow.
When the balance between reactive oxygen species (ROS, aka free radicals) and antioxidant defenses is disrupted, we can suffer from oxidative damage when free radicals prevail, but we can also suffer from reductive damage when an excess of antioxidant is present. This leads to several negative changes like mtDNA oxidation and damage to cell components, which are some of the many factors that play a role in the aging process and contribute to the hallmarks of aging and the development of degenerative diseases.
It’s important to understand that many scientists now argue that antioxidant supplementation is at best not useful and at worst damaging to our longevity and health. Unlike companies selling billions of dollars of antioxidants each year, it is not advisable to randomly supplement high doses of antioxidants unless indicated for some reason. Although we still have much to learn about free radicals, antioxidants, and aging, it is clear that the free radical theory of aging is an outdated theory, and we need to look at the bigger picture of multiple causes of aging.
Wear and tear theory of aging
The wear and tear theory states that cells and living creatures, like machines, wear out and that damage caused by radiation, accidents, diseases, toxins and harmful substances is accumulated over time until the organism can no longer function.
This is of course a rejected theory for many reasons, including the knowledge that our bodies have regenerative abilities, but when originally proposed by Wiesmann, german biologist, in 1882 it was a reasonable theory.
Programmed aging theory
The programmed theory of aging suggests that biological clocks influence aging by regulating the expression of genes responsible for maintenance, repair and defense responses. According to it, aging gives an evolutionary advantage: accelerating the turn-over of generations of the species promoting evolutionary change.
Mutation accumulation theory
The mutation accumulation theory, proposed by Medawar in the early 1950s, suggests that genetic mutations that are harmful and only expressed later in life, after the reproductive window, would have little influence on natural selection. As a result, these mutations would be passed down to future generations. In contrast, mutations that manifest early in life can impact fertility and survival and, if not beneficial to natural selection, would be eliminated. According to this theory, the accumulation of these mutations over time results in the aging process as we know it.
Error catastrophe (accumulation) theory of aging
The error catastrophe theory of aging, by Orgel in the 1960s, proposes that errors in protein translation due to mutations, which occur during the process of DNA replication, can accumulate over time and cause an increase in errors in protein synthesis. This accumulation of errors eventually reaches a tipping point, known as the “error threshold,” beyond which the cell’s ability to maintain its normal functions and repair its damaged DNA is overwhelmed, leading to cell death and ultimately to the aging of the organism. The theory was supported by the fact that mortality increases the older we get, but with further studies no evidence was found for an age-related increase in protein translation errors.
Neuroendocrine theory of aging
The neuroendocrine theory of aging proposes that as we age, there are changes in the production and regulation of various hormones, including growth hormone, cortisol, and sex hormones, which can contribute to age-related declines in physical and cognitive function. These changes can be influenced by various factors, such as genetic and environmental factors, and they may be exacerbated by lifestyle factors like stress, poor diet, and lack of exercise. The neuroendocrine theory of aging is still an area of active research and there is ongoing debate about the specific mechanisms involved and the extent to which they contribute to the aging process.
Immunological theory of aging
The immunological theory of aging proposes the fact that the decline of the immune system is a major contributor to the aging process. This theory proposes that as we age, our immune system becomes less effective in recognizing and fighting off foreign invaders such as bacteria, viruses, and cancer cells, leading to an increased susceptibility to infection and disease. This decline in immune function is due to a combination of factors including changes in the thymus, which is responsible for producing T-cells, and a decrease in the production of antibodies by B-cells. The immunological theory of aging also suggests that chronic inflammation (inflammaging), which is a common feature of aging, can contribute to immune dysfunction and accelerate the aging process.
Cross-linking theory of aging
The crosslinking theory of aging proposes that aging occurs due to the accumulation of irreversible chemical bonds, called crosslinks, that form between proteins and other molecules in the body. These crosslinks can cause stiffness and decreased elasticity in tissues, leading to problems with blood vessels, joints, and other organs. Normally damaged proteins are eliminated by enzymes known as proteases, but the cross-linking may make this difficult or not possible, leading to accumulation of dysfunctional proteins over time which results in aging and age-related changes in our bodies. One of the main ways cross-linking happens is through glycation, the attachment of a sugar molecule to a protein, which produces molecules known as AGEs or Advanced Glycation Endproducts, which attach to nearby proteins permanently and causes them to lose their function.
Cross-linking of proteins is one of the many factors currently believed to contribute to aging.
Rate of living theory of aging
The rate of living theory of aging is one of the oldest theories, with ancient philosophers believing that we have a finite amount of life substance and when it runs out, we die. This theory proposes that our metabolic rate determines the speed at which we age and that we have a limited number of heartbeats available to us, which is predetermined based on the amount of life substance. In the 20th century, this theory found support in the free radical theory of aging since a higher metabolic rate means more free radicals. The theory was also supported by the fact that some animals, like the giant tortoise, live over 100 years with very low metabolism, or that by studying reptiles, it was found that the higher the ambient temperature, the higher the metabolism, and shorter their lives. However, subsequent experiments have contradicted this theory, and it has been long rejected. Nevertheless, there are still studies that investigate the relationship between aging and metabolic rate.
Hayflick limit theory of aging
The Hayflick theory of aging, also known as the Hayflick limit, proposes that cells can only divide a certain number of times before they stop dividing and enter a state of senescence or programmed cell death. It was first proposed by Dr. Hayflick in 1961 who discovered that human cells can divide only approximately 50 times, after which they stop dividing.
Telomere shortening theory of aging.
The telomere shortening theory of aging suggests that telomeres, the protective caps at the end of chromosomes, play a role in the aging process. Telomeres shorten with each cell division, and when they become too short, cells can no longer divide and become senescent or die. This can lead to tissue dysfunction and contribute to the aging process.
Telomeres act as a buffer zone to protect the coding regions of the chromosomes from being lost during replication, and when they become too short, the genetic information can be lost. It was suggested that by reactivating the enzyme telomerase, responsible for the replication of the telomeric regions of chromosomal DNA, a cell could become immortal.
The telomere shortening theory has been supported by studies on various organisms, including humans, and is considered a major contributor to cellular aging. However, recent research has suggested that telomere shortening likely isn’t the only factor at play in cellular aging and that other mechanisms, such as cellular senescence and epigenetic changes, may also contribute to the aging process.
Disposable soma theory of aging
The disposable soma theory is one of the evolutionary theories of aging and puts in relation longevity with reproduction.
It was proposed by Kirkwood in the 1970s, and it suggests that organisms must balance their energy between reproduction and the maintenance and repair processes required for the cells of the body (known as the soma). If resources are invested in reproduction, there will be an accumulation of mutations and cellular damage, leading to a shorter lifespan. However, if reproduction is avoided until later in life, the organism can focus on maintaining its health and increasing the lifespan. This theory is supported by several facts. For instance, species that have a large number of predators, such as mice, may die due to predators before being able to reproduce if they invest in their soma. However, by investing in reproduction, even if not killed by a predator, they live a short life. In contrast, humans, with no natural predators, can invest in the soma and reproduce later in life without any evolutionary disadvantage.
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