Just like Hollywood movies, not all human beings age the same. It is not something that we have discovered in this century; we already knew it for a long time. But for a few years now it has become fashionable to differentiate chronological age , which marks our year of birth, with biological age, a fairly diffuse concept but which is usually defined as how old we are molecularly compared to a standardized model. And how is that done? Mainly by measuring the length of something we have on our chromosomes, the telomeres .
We must keep in mind that the cells of our body – and no cell, really – do not divide forever. In 1965 Leonard Hayflick discovered that there is a limit to the possible number of cell divisions, known today as the Hayflick limit, which in humans is around 50. As cells approach this limit, they show signs of aging. Apparently, this limit is linked to the shortening of a region located at the ends of the chromosomes, the telomeres.
It was A. M Olovnikov and James Watson – one of the discoverers of the structure of DNA – who found that there is an essential problem when DNA copies itself every time the cell divides. In order for the two strands to separate, what is called a first is necessary, something that gives the starting signal. In that case, the “shuttle” molecule is another nucleic acid, RNA. When its work is done it disappears, leaving in its place a hole in the DNA strand. This means that each time the DNA copies itself as the cell divides, the length of the telomere gets shorter. Nothing happens if we remove a little, because it is still there. It is the moment when practically everything has disappeared when we should start to worry; we have reached the Hayflick limit . We are aged.
TA 65: immortality in pills
Now there are animals, like the unicellular Tetrahymena , that repair their chromosomal DNA each time they divide: there is something that “fills in” the holes left. Blackburn and Greider found that the enzyme telomerase detects the shortening of the DNA strand and fills it in, making Tetrahymena immortal . Now, our cells also contain telomerase; at least some, like stem cells , which help make new cells of our immune system. The rest could contain it… if the genes were expressed. Why do not they do it? We do not know.
Hence, much research is directed to see how the shortening of telomeres can be prevented or slowed down. Among them, one takes the cake, the one that involves cycloastragenol or TA 65 , a substance that is extracted from the astragalus . In the early 2010s, some studies indicated that it prevented this shortening. It was not long before a number of companies began selling it as an anti-aging food supplement. However, no increase in mean life expectancy was found, but some physiological anti-aging effects were found without increasing cancer incidence. Of course, these investigations were in mice, not in humans. Hence, the US Federal Trade Commission said that it is false advertising to say that TA-65 can reverse aging and repair DNA damage in humans based on research that saw some effect in mice. That has not prevented it from being sold online as anti-aging pills.
Hormones to regain youth
On the other hand, the human body begins to “disconnect” when it is forty years old: it stops producing growth hormone, thecollagen, melatonin… It’s a biological response, nature’s way of saying you’ve already had to do everything you had to do in your life. Hormonal loss is a real part of aging. What would happen if a hormone was reintroduced into the body once we had stopped making it? Between the 1990s and the early 2000s, numerous studies were done to see its effect. Of all of them, two were the ones that obtained the most promising results: the one led by Daniel Rudman, from the Medical College of Wisconsin, and the one led by Étienne-Émile Baulieu, from the Kremlin-Bicetre hospital in Paris, who experimented with hGH enzymes,human growth hormone, and with dehydroepiandrosterone (DHEA) secreted by the adrenal glands. In both cases, an inversion was found in the evolution of certain biological functions. For example, in Rudman’s experiments, the volunteers – between the ages of 60 and 70 – regained 10% of their muscle mass and their skin thickened by 9%. This served to kick off the sale of the new anti-aging panacea, and the works of these scientists were cited without any decorum by the companies that sold the new (and scientific) elixirs of eternal youth. The problem? That we should not trust results that have not been checked and rechecked. So in April 2014 the magazineCell Metabolismpublished a study that revealed that, very possibly, what growth hormone treatments may actually be doing is the opposite: they are not anti-aging, but rather anti-aging. Life always reserves some macabre irony for us, and in this case it is with Rudman, a pioneer in the fight against aging: he died at the age of 67, 11 years below the life expectancy in the United States.
NMN, the magic bullet that repairs DNA
The search for the pill of eternal youth took a new turn in March 2017, when it was announced that a magical molecule capable of repairing our DNA from the errors that appear as a result of the passage of time could have been found. A team from the University of Wales came to that conclusion after a series of studies in mice . According to them, the magic bullet is the molecule responsible for repairing DNA from external damage, including solar radiation. It is called NAD+, it is found naturally in our cells and we lose it as we get older.
What the Welsh scientists found is that a precursor of that molecule, nicotinamide mononucleotide or NMN, improved the cells’ ability to repair DNA: “the cells of an old mouse were indistinguishable from those of a young one after a week of treatment ”, stated David Sinclair, lead author of the paper appearing in the journal Nature . “This is the closest we get to a safe and effective anti-aging drug that will be on the market in three to five years if the tests go well,” he said. That was enough: in less than six months, 96% pure NMN began to be sold at a price of 100 euros per bottle of 60 tablets.
One of them who is clear about it is the Belgian doctor Eric Verdin, president and CEO of the Buck Institute for Research on Aging , the largest private research center in the world that studies the causes of aging and how to combat them. Surely it will not surprise us to discover that neither Verdin nor the members of the board of directors are going to turn 60… For this expert, the research madness about aging was born in the 1990s when scientists realized that that aging was not inevitable. If aging is the fault of genomic problems, in the end it all comes down to finding repair proteins and turning them into salable drugs: “if there are pathways to regulate aging it means there are proteins, and that means that over time drugs can be developed.”
Now, he knows very well: “if you hear the word immortality, run away. There is no medicine that can give you that.” The best way to maximize life expectancy is to maintain a healthy body with good nutrition and exercise, which are “incredible anti-aging drugs.” Of course, other human beings are more of the opinion of the writer Oscar Wilde: “I would do anything to recover my youth… except exercise, get up early, or be a useful member of the community.” Everything has a price. If we want to live longer, there is something that has always been known and that works: reduce our food intake. Living longer means eating less… and less appetizing: ditch those fried eggs with sausage and switch to steamed broccoli. And not for a time, but throughout his life. And the earlier you start, the better.
References
RudmanD. et al, 1990, Effects of human growth hormone in men over 60 years old, New England Journal of Medicine, 32:1
Baulieu E. E. et al, 2000, Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue, PNAS 97 (8): 4279–84
Lu, Y., Brommer, B., Tian, X. et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature 588, 124–129 (2020)
