The Telomere Hypothesis of Ageing, The Rate-of-Living Hypothesis, Hormesis... this is the second article in my series of 2 about the ageing process. The first was Ageing & Death, Inevitable or Not?.
Telomeres are structures in the end of chromosomes. They protect the genes from being damaged during each chromosome replication. The telomeres, which are long at birth, become gradually shorter during life, since a piece is lost every time the cell is divided. If there would not be any telomeres, the chromosome itself would be truncated, with severe genetic damage as a consequence. Some researchers consider this telomere shortening, loss, and following damage as the only cause, one cause, or a contributing cause to degenerative disease, ageing and death. Indeed, telomere length might determine cellular lifespan.
Considering the telomere loss as the single cause of ageing and death is called the Telomere Hypothesis of Ageing. There are problems with that hypothesis, but we leave them at that, at least for the moment.
Telomeres can grow out again. An enzyme, telomerase, lengthens telomeres. And so do certain nutrients, meditation and exercise. The nutrients known to lengthen telomeres are vitamin D (in an optimal dose, both too much and too little have no effect on telomere length); folic acid, and omega 3 fatty acids.
Things known to accelerate telomere loss include alcohol, smoking, chronic stress, oxidative stress, and obesity.
At the present level of knowledge, telomere growth has proved possible only for some forms of cells. But there is no evidence that it would not be possible with all cells, if we can only figure out how. There is a lot of research going on about finding ways to reverse telomere shortening.
In theory, indefinite telomere preservation could possibly make the cell immortal, at least if we adhere to the Telomere Hypothesis of Ageing.
While studies have shown that short telomeres are connected to cellular ageing, declining immune system, and some other degenerative symptoms, the picture is not as clear about cancer.
When cancer develops, the cell starts to divide more often and by that the telomeres become shorter. The cancer cell compensates this by producing telomerase, the enzyme that stops telomere shortening and makes the telomeres grow longer. This is a survival mechanism of the cancer. If it did not happen, the telomere loss would kill the cancer cell. It could not divide more.
So, would suppressing telomerase be a way to kill cancer cells?
In a way yes, but the consequence on non-cancerous cells would be devastating. The whole organism would most probably die. For this to be a viable cancer treatment, the telomerase would have to be blocked selectively, only in the cancer cells, and there is no known way to achieve this. Not yet anyway. But in laboratory tests, one has used this method to kill isolated cancer cells.
No doubt, future research will bring more knowledge about telomeres, their role in ageing, and how to reverse the gradual telomere loss.
The rate-of-living hypothesis roughly states that the harder you live, the sooner you die. It means that the body wears out and you die, and the more you strain it, the faster you wear it out. This is as if the body was a dead thing.
If you have a hammer, it will wear out sooner the more frequently and forcefully you use it. Its material has a certain strength from the beginning, when it is used up, the hammer is worn out. For a living organism, such a hypothesis is absurd. But, although it has been scientifically refuted, it still has many proponents.
The second law of thermodynamics states that entropy must increase in any closed system. That is why an axe or a car must wear out by use. But a living organism is not a closed system. It has an input of energy and an output of waste entropy. It can – in various senses – grow, not only break down. This explains why the rate-of-living hypothesis is wrong.
Note that, according to the laws of physics, no ageing or death is necessary. However, living beings are not governed by physics alone.
A living organism is adaptive and responds to moderate strain and stress by growing stronger. If the rate-of-living hypothesis were true, all physical exercise would make us die sooner, and so would intellectual and mental strain. We would somehow consume our strength, and when it would be exhausted we would die. That is not the case. On the contrary, strain makes us stronger, strain keeps us young longer, and strains make us live longer. That is, reasonable and gradually increasing strain. But beware! There is always a borderline which not to cross, lest it becomes a matter of ”wearing out” instead. More is not always better!
This is analogous to the response curve of many chemicals and medical drugs. The benefit is not linear. (A linear response would be where more is indeed better, however high the dose is.) Instead they follow an inverted U (or biphasic) response. That means that the benefit is greater with increasing dose up to a certain point, then, when the dose continues to increase beyond that point, the benefit falls again, finally to entirely disappear. If the dose is then increased even more, the substance becomes harmful and sometimes lethal. Quite many substances follow that pattern. Even a environmental toxin as dioxine, which is classed as strongly carcinogenic [causing cancer], protects against cancer in very small doses.
Already in the 16th century, Paracelsus wrote “All things are poison and nothing is without poison, only the dose permits something not to be poisonous”. (This statement makes more sense than most people realise. Also ordinary things as water and oxygen, so necessary for our survival, are toxic if the dose is high enough. It might come as a surprise, but every year a few people die by something as prosaic as water intoxication.)
What if all toxins in small doses would trigger a “grow stronger” effect, although being harmful or lethal in high doses? Then the problem would be just to determine what is a suitable dose.
There is a word for this effect: hormesis. It is when there is low dose stimulation and high dose toxicity. Or, more general, when an organism or a cell shows an adaptive response to moderate stress. In this general form it includes (but is not limited to) the effects of exercise (physical as well as mental), limited energy intake (partial starving, fast, or low calorie diet), exposure to low doses of radiation and chemicals, ischemic preconditioning, and moderate exposure to temperature extremes. All these factors do indeed increase life-span. And I have previously described how the immune system needs exercise - that overcome illness, especially infections (untreated with antibiotics), make you stronger, provided they are not serious enough to kill you. (See: If You're Never Ill, You are Ill Indeed.)
Studies with heat and cold (although not on humans) have shown that extremes of either extend the live-span of “cold-blooded” animals and to some extent of mammals. It is easy to be mislead into thinking that, in the case of cold, it is a form of freezing effect, that the metabolism slows down. It does for “cold-blooded” animals, but for mammals (which includes humans) that would be to fall into the trap of thinking in terms of the “rate-of-living paradigm”. Indeed, metabolism increases to compensate for loss of temperature. What happens is that certain genes are activated by the cold and those genes increase the life-span. Reportedly, eating watabi, Japanese horseradish, triggers the same longevity gene that is triggered by cold. I have not seen any study confirming this though. But research is still in its infancy and most studies have been made on worms and rats. I'm sure we will see more results in the near future. This genetic mechanism, however, where a longevity gene is triggered by cold temperature, exists in humans as well.
For every compound (or form of stress or strain) there is the important threshold dose (or otherwise defined threshold level of stress) between the beneficial and detrimental range. It is easy to fall into the trap of considering it to be fixed. At least in some instances, it is not. Physical exercise is one example where the threshold is gradually forced upwards. Allergen immunotherapy is another. Perhaps we should consider the dynamic threshold a rule rather than an exception.
The Taoistic physicians of old China held the view that everything can be trained. Even the function of individual organs. They didn't have the same insights in chemistry and microbiology that we have today, but they might very well have understood the principle of hormesis without really labelling it as a principle at all.
What is the evolutionary function of hormesis?
Primarily, it serves the survival of, and regulates the size of a population. In a time of food scarcity, extreme climatic challenge, an epidemic, or any other straining condition, the weak members of the group die. There will be an increased number of deaths and the population will be reduced. This will be compensated, as the survivors will live longer. In their case starving, harsh weather, or overcome infection would have made them stronger, once they have come through it.
In the human body, this is most clearly illustrated by the effects fasting has on the cells. The lack of food makes the body literally eating itself. It takes waste and weak and sick cells. The harder the competition becomes, the more cells are consumed as energy for the rest. The strong and healthy survive - sick, aged and weak cells disappear. After the fast, only the strong parts of the body remain. The body as a whole is stronger.
Cell death, when the weak cells succumb, also triggers the growth of new cells – another compensation mechanism. Seen on the cellular level, the body is younger after the fast than it was before.
(This article is based on material previously published in Meriondho Leo 2016-2017, and in my e-book “Paradigms of Health”, 2019.)
Copyright © 2016-2017, 2019, 2021 Meleonymica/Mictorrani. All Rights Reserved.
(The lead image shows human chromosomes with telomere caps. Photo: U.S. Department of Energy Human Genome Program. Public Domain.)
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