The last 30 years have been decisive in understanding the molecular bases of the aging process, of that cumulative damage to our genetic material that makes us prone to suffering from deadly diseases that, today, we do not know how to cure. Although these advances are, for many, an exciting approach to the chimera of achieving eternal life, the objective of scientists today is to find the first treatment that allows cure age-related degenerative diseases. María Blasco is one of the most influential people in this field. The discovery of the telomerase in 1985 inspired her to dedicate her life to understanding, slowing, delaying or even reversing aging.
When do you think molecular aging begins in our body?
Aging occurs as soon as life occurs. From the beginning of an embryo there is a great process of cell multiplication to generate the individual that is born and then for that individual to grow to its final size. There is a lot of cell multiplication. It is a very critical moment and, there, any error that occurs, any problem that occurs can later result in, for example, having shorter telomeres than normal or that mechanisms that protect us from aging have not worked correctly and can lead to that we are more susceptible to diseases when we are older. That is, things that can happen in our mothers' wombs can determine the risk of diseases that we have as adults. Therefore, the aging process does not really begin when the first gray hair or wrinkles begin to appear or when a pathology has already appeared. It is these possible failures that can occur in the uterus that will later result in us developing diseases. Thus, the most critical moment to age well, and this is what is being seen now, are the first years of life and development and even intrauterine development.
Today, how can we intervene in molecular aging?
Many organizations have already been intervened in. The pioneering work was work on a worm called C Elegants. That was the first time that, by modifying genes, it was possible to see that longevity was modified. That was really a milestone because he wanted to say that aging could be modulated by genes. And, from there, there have been many works that have found different routes, different genes important for aging. In general, I would say that what we know is that there is no program for aging, there is no program for us to die. Nature has not selected genetic programs so that we grow old and die, but rather it has selected genetic programs so that we are young and healthy. What happens is that these programs decay over time, and whether they decay sooner or later, depending on the species, we think it has to do with how long this species survives in the wild. Therefore, the life span is adjusted with what is invested in those mechanisms that keep us young.
To what extent can aging be reversed today?
Aging can be reversed. What we did was show that we could slow aging and that mice that were chronologically old behaved like a young mouse. But it has also been done with other technologies such as cellular reprogramming. There are authors who say that this can also rejuvenate. The mechanism is darker because when it is reprogrammed, many things happen, we don't know exactly what. In the case of telomeres, we do know what happens: they lengthen. This has been shown to rejuvenate and slow aging. Telomere lengthening is a very clear, very clean technique. Telomerase only lengthens telomeres and when telomeres lengthen we know what happens. They do not trigger a persistent damage response and therefore cells can continue to multiply and tissues can continue to regenerate. When telomeres remain long, this means that a normal, mortal cell can be amortal. It is the only mechanism. There is no other that is capable of converting a mortal cell into an amortal cell. This is not achieved by any other mechanism, neither DNA methylation nor anything else. So, we know that it is a very powerful mechanism to confer extra life to cells.
What is your opinion on the ethics of genetic modification to combat aging?
I believe that modifying the genes of a species is something that is not ethically acceptable because it would be transmitting “superpowers.” But what can be done is manipulate the action of genes through drugs or through gene therapy strategies. It's what we have done. What we do is activate this telomerase so that the telomeres lengthen and we have seen that it makes the mice live longer, but not only that they live longer, but we can reverse it, stop aging diseases and this does not involve modifying the genes. Telomerase is expressed in an individual, he benefits from this, but his offspring, let's say, do not acquire this property of having telomerase.
Today, what are the main challenges that science is trying to solve in this line of research?
The great challenge of biomedicine today is to cure many diseases that are still there and that we do not know how to cure. Cancer is an example of this. There are some cancers that can be cured and that have a very high survival rate, but others that cannot, and when there is a diagnosis of cancer, we still do not have the tools to cure that patient. That is obviously an urgency and a priority, but the same for all other diseases of aging that are degenerative diseases. If there is Alzheimer's, if there is Parkinson's, if there is renal pulmonary fibrosis, a myocardial infarction... There is a lot of premature mortality due to degenerative diseases that we do not know how to cure.
In your opinion, how can society prepare for the challenges posed by an increase in the elderly population?
That is one of the great challenges that humanity has. I don't know how much work is being done to prepare for that challenge. I know that in the United States they are already making policies for this because, although they have a higher task than ours, they are already seeing that the birth rate is also decreasing, but Spain is a country that is going to have this problem in a very pressing way. I think that Spain and Italy and I don't know if Japan are the countries that will be demographically older in 2050. The best preparation, of course, is prevention. That is to say, this is going to increase the diseases associated with aging and the increase in health spending, etc., is already being noticed, because there are more and more older people. Therefore, the main emphasis will be on prevention, early detection of prevention and with better lifestyle habits and better screening capacity to detect diseases in time. And then also, obviously, to develop treatments that are curative.
How do you foresee this knowledge on molecular aging being applied in the future?
I think that the first thing that will come, since it is what many people are looking for and with a very high investment, is to try to get the first treatment, the first therapeutic strategy that can cure a degenerative disease based on the knowledge of why our cells age. . This can happen with telomeres and telomerase or it can happen with any of the other strategies that are now being considered. And once this happens, for me the second line of application of this knowledge will be that those people who are at risk of developing diseases because they have accelerated aging or because they have shorter telomeres, can prevent the onset of disease prematurely. . And as a third wave, in the future, perhaps it can be argued that why wait for a disease to occur. Perhaps we can have a longer, disease-free life by being able to keep our body young for longer. But the priority is to cure diseases. I think this is very clear within the field of aging.