Consuelo Borrás (Valencia, 1976) is a professor of Physiology at the University of Valencia and coordinator of the Healthy Aging Research Group at the INCLIVA Health Research Institute. For more than twenty years she has studied the molecular bases of aging, and the genetic and epigenetic characteristics of centenarians.
After her stays at the Center of Biology and Cardiovascular Medicine at King’s College London, the National Cancer Research Center in Madrid and the Einstein College of Medicine in New York, she was selected by the Science For Life Extension foundation as one of the 25 people in the world with an outstanding idea in the field of aging. Currently, Borrás, also a collaborator at CENIE (International Center on Aging), is also studying the possible role of stem cells and their extracellular vesicles as a useful tool for the regeneration of aged tissues. We took advantage of her time in Salamanca to participate in the Spain-Japan Longevity Summit to chat with her about all these issues.
What are you researching now? What does she work on?
We are working especially with regenerative medicine applied to aging. The latest thing we have done is use extracellular vesicles from stem cells from young mice, and inject them into old mice with the idea of ??trying to restore intercellular communication, which is one of the processes that is lost with age. We want to see if we are able to recover or improve any of the functions that are altered during aging.
Of the functions of the entire organism or some specific ones?
Fundamentally, we have studied muscle function with different functional tests, for example, how they coordinate, how long it takes to fatigue after running… Always with mice, we have not yet transferred it to humans. We take fat stem cells from young mice, from which we extract the vesicles, and we put them into the bloodstream of old mice. We have seen that they recover functionality at the muscular level and at the kidney level, which are two of the functions that are most altered with age.
What are extracellular vesicles?
They are like little balls that cells eliminate and that carry genetic components, proteins, metabolites inside… They carry communication signaling to transfer that communication to another cell. An example: a damaged cell can release these balls with information, saying “I am damaged, come and help me.” This regenerates the damaged cell. Another advantage is that these little balls can travel through the bloodstream and go from one side of the body to the other and regenerate any of the organs, or stimulate information that is valid for them, the cells, to regenerate.
What is the objective of all this?
The objective in humans, the most direct one that I have in mind right now, is that I would like to use these extracellular vesicles, mixed with an oil that is put on pressure ulcers in older people when they are in bed for a long time. It is known that vesicles can help healing.
Are there other possible applications?
We are seeing what the vesicles that come from healthy cells have compared to the vesicles that come from old cells, to check if we can isolate any of those components. In the very long future, we could design a drug that carries exactly the components that are inside the vesicles, or design synthetic vesicles that carry those components. Drugs or synthetic vesicles would be applied to everything that has to do with regeneration.
Talk about tissue regeneration… Could all this have ‘anti-aging’ applications?
When we think about aging and interventions to promote healthy aging, we are really thinking about two things. One, directly for longevity and another to delay the appearance of diseases associated with aging. The point is that we have gained a lot of longevity, but we have also increased a lot of dependency. Lately, rather than focusing on living longer, we are focusing a lot on living better. To do this we need to compress morbidity.
What does it mean, compress morbidity?
It is delaying the age of onset of any disease associated with aging. The most perfect example of this is centenarians, who at 80 years old do not have any disease. The idea is to try to simulate centenarians. In fact, we have done many studies with centenarians, investigating their genetics to see if we can simulate them. If an illness has to appear, let it appear as late as possible, because then you will be sick for a short time in your life. You are not going to modify your maximum life, but if you modify your disease-free years, you are gaining quality of life, which is what we all want.
It is said that in our hand it is between 60 and 70% of aging. Do you agree?
Yes. Our lifestyle greatly influences our speed of aging, because our genetics or gene expression can be modified through the environment, through epigenetics.
How does this work? What depends on whether some genes are manifested—expressed—or not?
You have DNA that you inherit from your parents. That DNA, depending on different factors, will be transcribed into RNA and translated into proteins and will be expressed in a function. The environment can modify, through epigenetics, the expression of genes, and therefore proteins and their functions.
An example?
If we are subjected to an environment in which it is very cold, the temperature is very low, more genes will be expressed that will protect us from those low temperatures than those that protect us from high temperatures. What we say is that people who are accustomed to the cold are actually because they have developed mechanisms that allow them to adapt to the cold, just like to the heat or any other situation.
This expression of genes is conditioned by the lifestyle that each person leads…
The expression of genes is marked on the one hand by genetics, obviously, but it is now known that it is also marked by the environment: lifestyle, climate, pollution…
Does the “environment” determine 60-70% of our aging, as some researchers have told Longevity?
Yes, approximately. What happens is that, for example, when we talk about maximum longevity, in our studies of centenarians, we have seen that the genetic load gains a little weight there. The genetic characteristics of centenarians are inherited to their descendants and that is why there are long-lived families that inherit those genetics. If you have parents and grandparents who have lived to be 100, the likelihood that you will live a long time increases.
Does that also mean that if I have parents and grandparents who have died at 60-70 I am more likely to die soon?
No, unless there is some genetic component that predisposes one to die early because it is related to diseases such as cancer, for example. I am often asked, “if I don’t have the genetic makeup of a centenarian, won’t I be able to reach a centenarian?” Yes, you can get there, but you have a better chance if you are a descendant of a centenarian.
I was talking about the cold… It is also said that exposure to unfavorable conditions can be positive for aging. What do you think?
I love that you asked me that question because I’m looking into that now too. There is a phenomenon called hormesis, which consists of us adapting to small stresses. That is wonderful because it means that when you have a small stress, of a small amount, if you are able to develop defenses against that stimulus, when a large stimulus hits you, you probably have more defenses than another person who has not developed those defenses.
Some example?
He always wears the image of Rasputin, who when he was imprisoned saw that his companions died when they brought them a specific plate of food. It occurred to him to eat the rest of the plate from which he died every day. When they gave him the big plate, he didn’t die. He had adapted to the poison. This is very important because we have a great ability to adapt to stresses when we are young or adults, but as we age, our ability to adapt to those stresses decreases. That means that when you are older, unless you are very healthy, any stress could have not a favorable but an unfavorable effect. It is my hypothesis that I am investigating now.
What does it mean, applied to daily life?
A clear example is physical exercise. Doing moderate physical exercise generates small stresses that allow you to adapt, thereby developing, among other things, antioxidant defenses that will protect you if you are later subjected to oxidative stress.
Do small discomforts make us more resistant?
Small doses of a stress to which you are able to adapt and respond, allow you to protect yourself from a much larger dose of that stress, and help you age better, because you develop defenses against the negative component. Physical exercise produces free radicals in small quantities that cause you to develop more antioxidant defenses. With age there is an increase in free radicals: those who have exercised have more antioxidant defenses than those who have not, because they are stimulating it little by little by generating a small amount of these radicals. That is, some small toxic inputs, small stresses, allow you to adapt to a much larger one, and can help you age better. Of course, once you are older, it is better not to subject yourself to many toxic inputs, because that ability to adapt is partly lost.
