Longevity, Part 4 When Breathing Kills: Free Radicals and Aging

In the last post we reviewed the shortening of the telomeres as one of the possible factors that lead to the aging of the body. However, the review would not be complete if we did not also examine another interesting theory regarding the origin of aging. This is the free radical theory.

In the last post we reviewed the shortening of the telomeres as one of the possible factors that lead to the aging of the body. However, the review would not be complete if we did not also examine another interesting theory regarding the origin of aging. This is the free radical theory.

According to this theory, we age as a result of ceaselessly performing the most basic action: breathing. As part of the breathing process, we consume oxygen. We need it to live, but the sad fact is that oxygen is one of the cruelest molecules we know. It likes to steal electrons from other molecules and destroy them. He does this so well that in chemistry the name 'oxidation' is given to describe the process of stealing electrons from one molecule to another. The oxygen is responsible for book pages disintegrating after many years of exposure to air, and it is capable of turning a solid block of iron into rust dust. A victim breathing pure oxygen for many hours would develop breathing difficulties, and when premature infants in incubators were exposed to high concentrations of pure oxygen, they went blind because the gas burned the retina in the eye. The explanation for all these phenomena is that oxygen creates free radicals as an inevitable part of the breathing process, and these damage the cells.

According to the free radical theory, aging is caused by the cumulative damage these molecules cause to cells over the years. We know for sure that free radicals are harmful to cells, and that the damage they cause is more common in old age. Moreover, the free radicals cause mutations - the DNA of each human cell absorbs about ten thousand oxidative damages every day, most of which are repaired, but some remain as they are. Old mice have about 2 million mutations in each cell. Young mice have only half that. The mutations can kill the cell, turn it cancerous or even damage the sperm and eggs and pass the mutations on to the next generation.

In short, there is no doubt that free radicals are not substances we want to come across in a dark alley. But are they the main cause of aging? There is still no consensus on this. There are interesting experiments such as those in which mice were injected with catalase - a human gene that breaks down free radicals inside the cells. The mice gained about 15% more longevity, mostly because heart disease and cataracts struck them later in life. The catalase protected the muscles and blood vessels against the free radicals. And that's nice, but you have to always and all the time remember that this is not 15% of the human lifespan - that is, more than ten years - but 15% of the mouse lifespan. I mean, several months. Suddenly that sounds a lot less impressive, doesn't it? And besides, what did they do anyway? Put human catalase into mice!

We can see that even in nature, long-lived plants are particularly resistant to free radicals, probably through genes called superoxide dismutases. Remember the flies that were blessed for long life? It turns out that they had a particularly strong version of superoxide dismutase. This experiment was repeated five times, and each time they found that this group of enzymes was increased in the long-lived flies. In another experiment, flies were genetically engineered to express human superoxide dismutase in their neurons - which is apparently more effective than the flies'. The lifespan of these flies increased by 40%. Similar results were also obtained in worms.

The gauntlet is thrown

And here is a question for you. Assuming that the genetic engineering treatment itself is completely safe: are you ready to have an extra copy or two of superoxide dismutase inserted into your cells?

I wouldn't be surprised if some readers nod their heads in agreement as an answer to the question. We all want to gain eternal life. But in this case, at least, you would be making a big mistake. Mutations in the superoxide dismutase 1 gene have been known in humans for years, which cause the enzyme to become hyperactive and work more than usual. We would expect such mutant humans to live to be 120 or older, but they die around age fifty from a brutal neurodegenerative disease that leads to general paralysis and death. In America, the syndrome is called Lou Gehrig's disease, after the famous baseball player who died of it.

Why does an enzyme that is usually so beneficial cause such severe disease when overexpressed? The simple answer is that no one knows. There are many guesses, and one of the best is that superoxide dismutase has an additional role in maintaining the structures of nerve cells. It is possible that SOD1 also plays a role in Down syndrome, where the child has three copies of the gene that codes for this enzyme, and the result, among other things, is mental retardation.

I hope you now understand better why we need to be so careful before we offer new treatments that have never been tested. The body is a complex and complicated system, and a change of one single gene can lead to devastating results.

And what about the most used medicine against free radicals: antioxidants? Many believe that taking antioxidants can help in the treatment of free radicals, but currently it is difficult to find good proof that this treatment results in a significant extension of life. If anything, the situation is the opposite: excessive intake of antioxidants can actually harm health.

There is still a long way to go

I don't like to be the prophet of the wrath of the bad news, but the bitter truth is that there have not yet been proven treatments in humans to prolong life. Beyond that, we are not even sure what the real reasons behind the aging phenomenon are, let alone how to prevent them.

Once we know what the real cause of aging is - free radicals, telomere shortening, or any other reason - we can treat it in a targeted manner. The shortening of the telomeres can be prevented through controlled and careful genetic engineering treatments that will result in the activation of telomerase in the body, but only temporarily so as not to disrupt the cell mechanisms. It is possible to fight free radicals in a similar way, by increasing the production of enzymes that break them down.

I don't want to sound too optimistic. Even if we uncover and decipher all the causes of aging, many more decades will pass before we can deal with them effectively. We have seen how complex the body's operating system is, and how careful we must be to play with it with our eyes closed. But these concerns should not cloud the final point: aging is a molecular process that occurs in the body, and there is no reason why we cannot prevent it in the future. For this, we will have to 'just' stand up against hundreds of millions of years of evolution, which shaped our bodies to be temporary. In doing so, we will continue the process of rebellion in nature that began when we used sharp stones instead of claws, and we used the power of fire to soften meat, as a replacement for the sharp teeth we possessed other predators.

Will the day come when we will be able to delay and even stop the aging process?

This question is unnecessary for me. This day will indeed come, of that I have no doubt.

The more important question, for me and for all of us, is when.

More of the topic in Hayadan:
"Longevity" series by Dr.Roey Tsezana
Longevity - Part One: The Road to Eternal LifePart two - the evolution that killed me
To stop death - third part in the series, "longevity of life": the hunger for life
Longevity, Part 4 When Breathing Kills: Free Radicals and Aging
Keeping death at bay: the telomere theory. Fifth article in the longevity series

Towards an immortal life by Dr. Aharon Hauptman