Why do we age? Why do we die? These questions are one of humanity’s greatest challenges. We can see it in religions, which have created different justifications for death; or the large number of myths about a Fountain of Youth.
We cannot explain what aging really is without turning to the concept of evolution. As the geneticist Theodore Dobzhansky said: “Nothing in biology makes sense except in the light of evolution.”
The basic mechanism that evolution uses to cause changes in organisms is called natural selection: the different characteristics that individuals of the same species have will define their probability of reproducing and surviving. This means that, natural selection will preserve the traits of the individuals that favour their survival. As a result, their characteristics will adjust to the environment in which they live. If natural selection is trying to guarantee species’ survival and reproduction, why does death still exist? And aging, which apparently does not mean any benefit?
The answer is simple: it is beyond the species’ capabilities to avoid their death1. The explanation of this needs a little more detail though… Let’s focus on nature: the cause of death of the vast majority of organisms is totally external to themselves. It can be due to predators, pathogenic infections or accidents. This is known as extrinsic mortality. This mortality defines a period in the life of an organism, its youth, where it has high chances of being alive and, therefore, where its reproductive stage is concentrated.
The resources we have in order to stay alive are limited: we acquire a certain amount and distribute it according to our needs, creating a trade-off between body maintenance and reproduction2. If we dedicate all the resources to preserve our body, there is nothing left for reproduction and vice versa.
To respond to this trade-off, we focus the resources for reproduction in the first period of life, where the vast majority of individuals are still alive. In this way we make sure that our genes pass on to our descendants. Once this period is over, the body is no longer optimal for survival. It is as if we had sprinted and were left with a tired and exhausted body. Furthermore, most individuals will have already reproduced after a certain age, and then the force of natural selection reduces drastically. The scientists Medawar, Haldane and Williams defined this idea in the second half of the 20th century, using mathematical models3.
We see that our body is prepared to be at its best for a certain number of years, during our youth. Whatever happens after reproducing does not matter to evolution. That is the reason why we are left drifting in a period known as aging. A quote from the research professor at the Catalan Institution for Research and Advanced Studies at the University Pompeu Fabra, Arcadi Navarro, summarizes it: “Natural selection prefers healthy young people, even if the price to be paid is sick adults”. If we want to find the Fountain of Youth, we must overtake evolution.
PROGRAMMED CELL DEATH or APOPTOSIS – The machinery of self-destruction
A curious case in relation to death is apoptosis: a process that happens inside our cells and causes their self-destruction. Although it may seem harmful, apoptosis is necessary for our survival. For example, it allows multicellular organisms like us to “punish” cells that rebel against their specific function, guaranteeing a correct coordinated functioning of the entire body. We know this rebellion as cancer. In front of a potentially carcinogenic cell, a control system is activated that triggers apoptosis and destroys the threat4.
When did we acquire a machinery that causes our own cellular death? The answer to this question is fascinating, as it has its origin in single-celled organisms, where apoptosis kills the only cell they have. Phytoplankton are single-celled organisms that live in colonies and exist for 2.8 billion years. They captured the machinery for apoptosis from the viruses that infected them. Although it was a tool for virus survival, the infected cells learnt how to take advantage of it and used it against them. When the cells were infected, they activated apoptosis and caused self-destruction, destroying the viruses inside along with them. By doing this, they prevented the viruses from spreading throughout the entire colony5. As the Catalan writer Salvador Espriu says in his poem La pell de brau: “Sometimes it is necessary for a man to die for its community, but an entire community should never die for a single man.”
The evolutionary background that we have seen explains the existence of aging at the level of entire individuals. But what happens inside us when we grow old? How do the cells in our bodies age?
One of the most accepted theories that explains cellular aging is the mutation accumulation theory. Throughout our lives, cells divide to form new ones. During this process, they copy their genetic material and sometimes errors occur. Most of these errors are detected and reversed in some way. But as we get older, all the errors that have been accumulating pose a risk to the cell6.
If you want to know the other theory that explains cellular aging along with the mutation accumulation one, you can check it here.
In this image you can see the telomere regions (pink) at the ends of the chromosome. “Telomeres on a chromosome” © AJC1 | CC BY-SA 4.0
One of the most studied causes of aging is related to telomeres. Telomeres are the DNA regions at the end of each chromosome. Their function is essential, since they protect the rest of the genetic material from being degraded.
The repair machinery of the cell could mistake the end of a chromosome for a cut in the DNA and try to repair it. To prevent this from happening, what telomeres do is to fold the DNA strand into a circle to close it, thus hiding the end. With each replication, telomeres shorten due to the replication mechanism itself, which leaves one of the DNA chains unfinished. When the telomeres reach critical length levels, the cell activates signals to prevent it from further dividing7. The telomeres are a clear example of the error accumulation theory that exists throughout our lives and that ends up damaging our bodies when we grow old.
There is a protein called telomerase, which function is lengthening telomeres. But telomerase is only found in certain cell types (such as stem cells). Why is it not in all the cells in our body? It turns out that the telomeres shortening has its benefits too: it is a control barrier against cancer. Cancer is an aging-associated disease, since its frequency increases with age. For tumours to form, certain errors must accumulate in one cell’s DNA. To decrease the probability of this accumulation, cells have the telomeric “barrier” that limits their divisions. Therefore, a price to pay in order to avoid cancer is getting old.
A recent study from 2019 has verified that the rate at which telomeres shorten can be used to predict life expectancy8, compared to the outdated belief in which it was calculated with the initial telomere length.
“Friends eating lunch in diner” – By Dan Gold © Unsplash | CC BY 4.0
There are many studies that look at the relationship between food intake and aging. The signalling that is activated in cells when we eat is linked to our metabolism and, therefore, to our body changes. If these signals are increased, aging could be accelerated. But the opposite is more interesting.
It has been found that reducing caloric intake in mice without reaching malnutrition levels can prolong life expectancy by up to 60%. The same happens with many other species, such as fruit flies or yeast. What’s more, caloric restriction not only does extend lifespan, it’s been seen that in old primates this restriction decreases the risk for diabetes or cardiovascular diseases9.
The signals that activate in cells when we eat have been studied and it was found that a gene called TOR (target of rapamycin) is one of the most important ones. Reducing its action can eventually extend the lifespan of the studied mice. This is achieved by protecting the mice from cancer or delaying body atrophy10.
One might think that the complete deletion of TOR would imply numerous benefits, but this gene is essential in many signalling routes that occur in our body, such as during development. Nevertheless, TOR inhibitors such as rapamycin are being studied to find out their association to longevity. It is still soon to say, since rapamycin has side effects, like testicular degeneration11.
We always have the option of cutting down our food intake in order to live longer. But surely many of us would not be willing to make this sacrifice.
We have seen that aging is nothing more than a side effect of evolution: evolution is merely interested in having young individuals as fit as possible to reproduce. So, ageing is hidden under its shadow.
We have seen what ageing really means inside our bodies: a shortening of telomeres and an alteration in the intake signalling. But there are many other causes behind it12. Ageing is the accumulation of errors that occur in the cell and that will eventually manifest.
Today’s medicine tries to fix every illness that appears due to ageing, such as arthritis, dementia or diabetes. But to stop growing old, we would have to eliminate the problem from the root. We would have to beat the game to evolution.
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