María Blasco: “Telomerase is an antidote to aging”

Some debate whether aging is itself a disease. But, there is no doubt that by facing it, we can prevent, delay and even avoid age-related diseases, including cancer, pulmonary fibrosis, aplastic anemia or myocardial infarction. Scientific advances are showing that prolonging youth with a good quality of life is possible.

A little over 10 years ago, a group of researchers reviewed what was known until then about aging and published their analysis in an article in the journal Cell, which had a great impact on the scientific community. The team of experts identified at least nine molecular indicators of aging, that is, measurable processes that accelerate or slow down the deterioration of the body with age. They spoke of four “primary causes”, all closely interconnected. One of them refers to the shortening of telomeres, structures found at the ends of chromosomes that protect the genetic material.

María Blasco is one of the three Spanish authors who participated in the Cell article and is the one who can best tell us about telomeres and their role in aging. Specialized in biomolecular research, she has dedicated more than 25 years to studying them, becoming one of the leading Spanish scientists and most recognized nationally and internationally.

His findings in the field of aging are joined by the direction of the National Cancer Research Center (CNIO), since 2011, which has allowed him to relate the behavior of telomeres not only with aging, but also with cancer and other diseases. degenerative diseases.

Why is aging such a powerful object of study today?

For some decades there has been more and more interest in understanding it, because it has been recognized that the origin of most of the diseases we have when we get older is due to the aging of our cells, our organs and tissues and, ultimately, of our body. In other words, aging is at the origin of many diseases that kill us. The only way to prevent them is to thoroughly study their causes.

When we turn years old, we see obvious physical and cognitive changes, wrinkles, kilos and ailments. You, however, put the focus on telomere shortening. What are they and why are they the children of your eyes?

In 2013, several researchers, three of them Spanish, among whom I have the honor to include myself, published an important essay in the prestigious scientific journal Cell in which we explained why we age at a molecular level. One of the fundamental causes is the shortening of structures that protect our genetic material, called telomeres, which are found at the ends of the chromosomes, where the DNA is found. To explain its function, we have to think that life is designed in an imperfect way and, when there is cellular damage, to repair it, two cells have to be generated from the damaged cell, copying the genetic material. So, every time the body is damaged, it starts a repair process, in which the telomeres shorten little by little. This event, which, on the other hand, happens all the time in our body, is what allows the body to regenerate.

What is the aging mechanism exactly?

It is known that when telomeres are very short they are capable of triggering aging, poor cell function or poor tissue regeneration, diseases occur and, ultimately, they can cause death. It is one of the primary causes of aging, which are called that because, in turn, they are the origin of other factors that cause us to age.

To the term telomere, we add telomerase…

It is an enzyme that is a molecular machine, an antidote to this shortening. This occurs when we are embryos: it lengthens the telomeres of the embryo to have a long and healthy life, but it goes to sleep, turns off or silences when we are born. Therefore, there is no telomerase in adult life and hence telomeres shorten each time cells replicate to regenerate tissues. Making telomerase work in the adult organism is enough to lengthen the telomeres and increase longevity or the time of youth. But we have also seen that it serves to treat pathologies associated with this aging. We are trying to generate therapies for degenerative diseases with a gene therapy based on telomerase.

Is the dormant telomerase activated or a new one added?

The dormant telomerase of the cell is not touched, but with gene therapy, which consists of producing telomerase again in the cell, it can be directed towards the cells we want and thus have therapeutic effects in different diseases.

With it, you have extended life in the laboratory…

Yes, we have extended the life of mice by 40%. We think that telomere shortening is one of the primary causes of aging, and that the action of telomerase is a way to prevent it. We have detected that mice with longer telomeres live younger for longer, but we have also seen therapeutic effects in diseases caused by short telomeres. Then, the progression of cancer or other degenerative diseases such as pulmonary fibrosis can be stopped, which is one of the important consequences of people who have suffered from covid. Other diseases associated with short telomeres that we are working on are renal fibrosis, myocardial infarction and aplastic anemia (the bone marrow is not capable of regenerating blood).

Any chance of extending human lifespan further?

We have done it several times in animal models, but our priority at the CNIO is not to extend life when we are healthy, although it would be interesting, but to cure degenerative diseases, because we still cannot cure them, we do not know how to stop pulmonary fibrosis, a disease of kidney or heart. However, we have data that says that with telomerase we could do it.

Extending life is the same as delaying aging, but shouldn’t we also talk about quality of life?

Quality of life is implicit. When we refer to telomerase, we do so to live longer, because there would be fewer diseases and because we would be young for longer. The equivalent would be, to give an example, that at 80 we would look like 40. It is not about extending our life by getting older, which is what is happening now and why so many diseases appear, but rather about being young for longer. time. That, as far as preventing aging; But let’s not forget that the idea is to treat degenerative diseases, stopping them, remitting them or reversing them, rejuvenating the cells.

Is cancer a luck thing, a lottery as some say?

One of the basic properties of cancer is that tumor cells are capable of multiplying indefinitely, because they maintain their telomeres in an aberrant manner and, at the same time, their telomerase is also awakened in an aberrant manner. Cancer is natural proof that telomerase is sufficient to maintain cells forever.

So are cancer cells immortal?

Of course, they would be immortal if we didn’t kill them. But, in a scenario where they have food and we let them multiply, they would do so indefinitely. In fact, the first tumor cells that were isolated, back in the 1950s, are still being replicated in all laboratories around the world. They are known as HeLa cells, after Henrietta Lacks, a woman to whom they belonged and who suffered from cervical cancer. So, cancer cells are proof that the maintenance of telomeres and the action of telomerase is nature’s way to regulate this capacity for indefinite multiplication. What we try to do with cancer is rob it of that immortality. At the CNIO we are working on destroying their telomeres, through chemical molecules, as a therapeutic window that allows us to do so without affecting healthy cells.

Could we ever stop aging?

No one has managed to stop aging, but it has slowed down a lot. Aging is not obligatory in nature. There are species that never age or are potentially immortal; others that live hundreds or thousands of years. There is nothing in biology, physics or chemistry that puts a limit on the ability for two cells to emerge from one cell. Humans are by no means the longest-lived, but we are trying to find out what regulates this longevity to live longer and better in the future, and, of course, how to prevent degenerative diseases.

Delaying aging is not the same as rejuvenation, which would be recovering lost youth. What does science say about whether we could regress in old age?

We have seen in mice that it has been possible to eliminate degenerative diseases to remit them, which would be like going backwards or the equivalent of rejuvenating. But this could be done to a certain extent, since if an organism is very damaged or aged, it would be very difficult to go back. I think it would depend on the moment in which it is done. In the laboratory, in our research, we have seen that the younger we treated the animals to maintain longer telomeres, the greater the effect on longevity because we delayed all the pathologies associated with aging, including cancer. That’s why they lived longer and were healthier for longer.

In humans, there are those who live more than 100 years, are we physically and mentally prepared for that much?

If there are people so long-lived, it is clear that they do. The length of life depends on the state of health of each person. It is true that there is a certain genetic component that affects. For example, a defective telomerase will mean that our telomeres will not be maintained as well after birth, so we will suffer more quickly from any of the diseases that are associated with shorter than normal telomeres.

The idea is to live longer and better, what is in our hands to do it?

Even if we are born with a normal level and quality of telomerase, any lifestyle habit that is going to cause damage to the body will force our cells to regenerate more times, which will cause the telomeres to shorten more quickly. The more we damage our body with unhealthy habits such as smoking, a sedentary lifestyle, poor diet or alcohol, the more we force healthy cells to multiply more frequently to regenerate tissues. This, as we have said before, will mean that we will be left with shorter telomeres or even without them, which will accelerate aging and prevent diseases.