“I studied medicine with the idea of ??research, not of seeing patients, I get dizzy seeing blood! During my degree, a specialist in physiology suggested that I work in the laboratory. “That was the best thing that ever happened to me.” Passion for the microscope, the laboratory, the hypotheses, the data… That is what Ana María Cuervo feels, a cellular biologist born in Barcelona and trained in Valencia and the United States, who is now a world leader in the field of aging. and specifically in autophagy, the self-cleaning mechanism of cells.
Cuervo, co-director of the Einstein Institute for Aging Research in New York, and a senior professor of Molecular Biology, was co-editor-in-chief of the journal Aging Cell for 14 years. Additionally, she has held a seat on the Panel of Scientific Advisors of the US National Institute on Aging (NIA), and is a member of the American Academy of Arts and Sciences and the National Academy of Sciences. Sciences. She attends to La Vanguardia, with a contagious enthusiasm, from her office in the Bronx, New York.
She has spent her entire life as a researcher dedicated to aging. Why this fascination with this topic?
When I finished my degree in Medicine, I requested to do my thesis at the current Príncipe Felipe Research Center in Valencia, the Cytological Research Institute at that time. Of all the rotations I had done in medicine, Geriatrics was the one that seemed hardest to me. At that time the idea was to keep the elderly patients as comfortable as possible, but everything was considered lost. I was interested in knowing why we age, and doing something about it. At an open house I attended, scientist Erwin Knecht said the word aging. When I heard it, I jumped into it.
He left for a few months and has been researching on the front lines in the United States for 30 years. Since 2001 he has led his own laboratory, The Cuervo Lab, at the Albert Einstein Institute in New York… What exactly do they study?
10 years ago, all researchers on this topic on both sides of the Atlantic met to see which factors are most important in aging. I have focused on autophagy, cellular cleaning systems. In our laboratory we see how they change in physiological aging, in animals or general population samples. We study centenarians and their children, who have a predisposition to longevity. We also have three areas focused on aging diseases: neurodegenerative (Alzheimer’s, Parkinson’s, macular degeneration…), metabolic (diabetes, obesity, arteriosclerosis, loss of muscle mass), and cancer. We see how cellular cleaning systems, when they do not work well, contribute to these diseases and how some of the interventions we do to improve cellular cleaning could be applied to this type of pathologies.
What does this cellular cleaning, the autophagy, that you investigate, consist of?
It is the mechanism by which cells clean what they have inside. Cells generate garbage, damage, and components that do not work remain there. The cells put the damaged material into bags, like small garbage bags. It is actually the best recycling system in the world and it happens every day in every cell of your body: when they find what is damaged, the cells break it into parts and reuse the pieces that are functional. Breaking down or eliminating this garbage is coordinated with the energy needs of the cells or individuals. When you don’t have food, they look for what they can eliminate to recycle and produce energy.
Does that mean that autophagy is activated when there is no food intake, when we do not eat?
Autophagy increases or becomes more “motivated” when you do not have food. A factor that we often forget is the importance of sleep, we abuse little sleep, and cleansing occurs when the cells are functioning relaxed. A merchant does not start cleaning his store when he has all the customers in his way, he cleans when he closes! Well, the brain cells think the same: when they go to sleep there is reduced neuronal activity, and this cleaning is induced there. But since in our society we eat continuously and do not sleep, we have to look for motivational formulas for the cells to clean.
How many hours do you have to sleep for autophagy to work well?
We are very unique individuals with different genetic backgrounds. Each one will have the maximum benefit with a certain amount, but seven or eight hours of sleep would be best for efficient autophagy.
Does fasting for a few hours a day, hourly calorie restriction, work to improve autophagy?
Not only autophagy, speaking of aging in general, it has been known for more than 70 years that if you reduce the number of calories to 60% of what you normally eat – an outrage – animals live longer, are healthier, have less spontaneous diseases. Eating 40% less food will not be the solution, but experimentally it is great. When implementing it in society we have to be realistic and this cannot be achieved. That is why many studies have been done in two directions: the mechanisms by which this reduction slows aging, and what type of nutrients and times of separation between meals are best.
What has been seen about nutrients, type of diet, and aging?
A balanced diet is always best. Dr. Dolores Corella, at the University of Valencia, studies the beneficial effects of the Mediterranean diet and has found that it is one of the best for longevity and functionality (what we want is to avoid fragility or deterioration). The other aspect, easy to implement, is to observe the times at which we eat. Autophagy is activated when there are no nutrients. There are two types of cellular cleaning: one is activated after 4 or 6 hours without eating – the one that cleans with the duster -, the other is activated after more than 10 hours without eating – the one that cleans thoroughly with the vacuum cleaner -.
Is the idea to separate meals a lot?
Yes, the idea to improve autophagy and delay aging would be to eat twice a day. At eight o’clock and at sixteen o’clock. Each one can organize it differently, but for example, skipping breakfast, eating at one in the afternoon, and then having dinner at nine is something easy to implement. You can also start with a strong breakfast, and then have an early dinner. This is very important to consult with doctors, because there may be underlying conditions for each individual, for example pre-diabetic or hypotensive people, who need other schedule guidelines and the doctor is the one who must advise. Now there are studies that say that depending on your age, you benefit more from some meal patterns than others.
This is difficult, they are very spaced meals… Should we feel hungry for autophagy to be activated?
The body gets used to it and there comes a time when you don’t feel hungry, but you simply eat less. The interesting thing is that you don’t have to reduce your daily calories, you can eat the same thing you usually eat, but separated into two meals. We must emphasize that this is not a diet to lose weight, the objective is to keep blood sugar and fat levels well controlled, so as not to have peaks. Of course, if you eat 2,000 calories a day of refined sugars, it won’t work; The diet must be balanced.
His research on autophagy has even interested Bill Gates, who invited him to talk about it! How was the?
The meeting with Bill Gates was a few years ago. He was interested in learning more about autophagy and the possible implications for the treatment of neurodegenerative diseases, as he wanted to launch an initiative to advance new treatments in that area. So he invited me to visit him and his team at their offices in Seattle. I had been “trained” a lot on how to maintain a formal visit, but two minutes later he started with very interesting questions, he is super quick mentally! I forgot to be formal and we both ended up leaning on our elbows on the table looking directly at other data that I had not included in the presentation. It was a very pleasant experience.
Is aging a disease? It is one of the big questions…
We have to change the mentality of the regulatory agencies a little, because in principle for me it is a physiological state, like adolescence, for example. We must give a positive meaning to the idea of ??growing old: when you reach an age you have already fulfilled a professional level, you have already paid for the children’s school, you have the experiences of having interacted with a lot of people during your life and you are in the best moment. The only thing that fails us in all of this is the loss of functionality, which is what we are trying to compensate for. Now, the regulatory agencies for clinical trials and drugs only approve studies if it is to treat a disease, not a physiological condition.
And do you study anti-aging drugs that are slowed down by that?
At our university, studies have been carried out with metformin, one of the drugs for diabetes, and it has been seen that it has beneficial effects even in the general population. There was a study in the Nordic countries that showed that diabetics who are taking metformin aged less than the general population despite being diabetic. Many experimental studies have now been done, it is one of these types of interventions that acts on several of the pillars of aging, including cellular cleansing… When proposing a clinical trial at the general population level to test it, the idea would be, Once over 50, test metformin in a diverse population. The biggest problem is convincing the clinical trials regulatory agency (FDA) to approve it, for them aging is not a disease.
Institutions, then, are slowing down drug research, then?
We have to change the mentality of drug regulatory agencies, now that there are possibilities to intervene and that there are many successes, at an experimental level, in slowing down the aging process. Modulating it has to be considered as part of the pharmacopoeia and part of preventive medicine.
What effects do you think metformin could have on aging?
The first thing is that metformin could prove that it can intervene in aging or that the speed at which we age can be modified. Second, that it is applicable to the general population, it would be a way of seeing that at the general population level the intervention with metformin has an effect, because what we can do in the laboratory never includes the diversity that you have in the population.
Manel Esteller told us that in about ten years we will have specific drugs to slow aging… Are you going here?
I share Manel’s optimism, although it is risky to say a specific deadline, everything takes a little longer than one wants, but there will be drugs and interventions so that aging does not progress as much or at least to maintain functionality in older people. It is not going to be the magic pill, but ideally there will be a small library of compounds and depending on your particularities, with precision medicine, when you get to your annual age checkup, they can measure how your pillars of aging are: your telomeres, your cleaning… They will give you a combination to help you age in a healthier way.
It will be personalized, but not universal. Who will benefit?
In addition to drugs, there is a lot of emphasis on interventions such as sleep, separation of meals… With this it could be much more universalized, because if not we can only do it in developed countries.
Is more than 50% of aging in our hands, in each one of us, as many specialists say?
In aging there are three pillars and the first is genetics, you cannot change your parents and grandparents. The other two parts are the environmental and the metabolic, life habits. There is nutrition, separating meals, exercise, rest, social interaction… In the environmental component, it is where we need big policies, because everything we are continually exposed to is out of our hands and more so at the level of population and governments and other things. What we have left is to really work on the part we can, which are the changes in our lifestyle habits, 30 or 40% of the total, surely.
Regarding exercise, what should be taken into account to age better?
We have a very sedentary life and getting out of that is already a huge step forward, even if it is only a half-hour walk. Moderate exercise has many benefits. For this there must be a change in personality, we are not going to have the time to be in the gym every day for an hour. So we want recommendations that are really practical, now that the activity bracelets are worn, getting up from the chair to go drink water, now counts as daily steps, how to move, stretch your muscles, walk around the block… What At the end of the day, when you go to bed, you have completed a number of steps, and increasing it becomes self-motivated. The body asks you for what it needs.
Social interaction is also key, he says. Up to what point?
We don’t value it, but meeting friends and talking, or even WhatsApp, is essential. We must make the effort to provide our elderly with frequent personal interactions and leisure activities. You have to involve them in family life, that type of incentive is super important. Once you lose the interaction, cognitive deterioration accelerates exponentially.
What do you think of the biological age clocks that are already common in the United States? Are they effective?
One of the scientists who developed the first clock, Steve Horvath, is a very good friend of mine. This watch tells you your biological age, which is not what it says on your ID card, by analyzing a bit of DNA, for example with saliva. It is based on what is called epigenetics, and although it has a good correlation to openly generalize it for the population, it is like looking at aging through a small channel. You only know how you are with respect to certain epigenetic marks, but how are your telomeres? How is your energy system? How is your cleaning system? We are working to correlate their clocks with ours.
When will we have these global biological age clocks?
During the next five years, biological clocks will be released because that is what many of us in this field are researching. Here, the National Institute on Aging (NIA) or foundations like Hevolution have begun to create these interest and work groups, where we will evaluate the real time clocks that come out and how they are applied.
