While studying Medicine, Ana María Cuervo (Barcelona, 1966) already knew she didn't want to have a medical practice but rather focus on research. She just needed a starting point. She found it after rotating through different medical specialties, including Geriatrics. "At that time, the idea that stuck with me was that nothing could be done about the problems caused by aging," she recalls. "And since I'm someone who always tries to fix everything, I wanted to research in that area."
Today, over 30 years after that decision, Cuervo is one of the world leaders in longevity research. She co-directs the Einstein Aging Research Institute in New York (US) and is a reference in studies on cellular cleaning, a process with a significant impact on how we age.
She recently received the Jiménez Díaz Commemorative Lecture Award in Spain, an award given annually by the Conchita Rábago Foundation to outstanding researchers in the field of Medicine and Biology.
Her goal, she emphasizes, "is not to eliminate aging but to change the way we age."
"What concerns us all about aging is the loss of functionality and health. If we aged and were just as functional and healthy as when we were young, no one would worry about aging. In fact, growing old can be the best stage of your life. A time when you no longer have to worry about your career or your children and you have all the experience that years have given you. What prevents us from enjoying that is having more ailments, more health problems, and being more vulnerable. That's what we want to change, how we age," she emphasizes using what she herself defines as "broken Spanish", a result of the decades she has lived and worked in the US.
Question. Why do we age?
Answer. We age due to multiple causes, there is not a single reason. In 2013, 10 pillars of aging were formulated, a list that some expand to 12 and includes factors such as telomere shortening, loss of stem cell activity, mitochondrial dysfunction, intercellular communication, or cellular cleansing loss, which is what we work on, among other issues. Aging is always multifactorial and personalized. Some individuals may experience telomere shortening first while maintaining good cellular cleansing, while for others it may be the opposite or other factors that contribute more significantly. The current focus is on developing gerotherapeutics, an approach that allows for precise and personalized aging modulation, addressing each case. Just as when you go to buy clothes, you don't just pick anything off the rack in any size, but rather look for something that fits you and your needs. The same goes for aging. Many people see promises online and buy whatever for aging. But before intervening, we need to understand why you are aging and which of these multiple factors affect you the most.
Q. Is it possible to assess the state of different parameters related to aging through biomarkers, as done with some diseases?
A. One of our goals is that, just as at a certain age you undergo routine gynecological tests or a mammogram, in the future you could also undergo an analysis that tells you the state of your mitochondria or cellular cleansing systems in relation to aging. Different groups are searching for blood biomarkers that indicate these cellular processes. One limitation we have now is that we have not yet established the baseline, we do not have enough population data to identify what thresholds are considered normal. However, clinical trials are starting with interventions to change the aging process, and these studies will provide a wealth of information.
Q. Your work group focuses on cellular cleansing systems. Do these systems that we have to clean our cells stop working well as we age?
A. Like any house, cells also need to clean themselves inside, recycle, and remove what accumulates and is not needed. When you are young and healthy, this happens every day in all cells of your body. What we have found is that as you age, part of the functional losses in the cell are related to losses in this cleansing system. Our laboratory focuses on three major groups of age-related diseases, metabolic, neurodegenerative, and cancer, and we want to analyze if changes in this cellular cleansing improve the outcomes and prognosis of these diseases.
A cleaning issue
In animal studies, the group led by the scientist - the "little crows," as they call themselves - has shown that if this system is eliminated in a young animal, it ages more. Conversely, when this cleansing system is restored in an old animal, the individual ages less, is less fragile, and has better functionality in multiple organs.
In mouse models of Alzheimer's disease, the use of activators of the cleansing system they are researching - chaperone-mediated autophagy - improved memory, eliminated depression symptoms, and drastically reduced protein accumulation in the brain. A similar strategy also worked in models of atherosclerosis, the cardiovascular disease that causes plaque buildup inside the arteries.
"At the moment, we can treat a mouse, but we still cannot do it with a person, but the studies tell us that we are heading in the right direction," the researcher points out.
Her work revolves around the key importance of cleansing for the functioning of any cell. Many age-related diseases, such as Alzheimer's, Parkinson's, or myasthenia, are due to the abnormal folding of a protein that starts to accumulate, she explains. "This abnormal folding occurs from a young age, but it does not cause problems because the cleansing systems work. The chaperone is like the quality control manager of a factory, indicating what is wrong and needs to be recycled. But as we age, the recycling system starts to malfunction, causing the protein to accumulate and eventually affecting cell function. The symptoms of different diseases are different because the protein causing them is different, but the cause is the same, a cleaning problem."
Being able to modulate and restore this system when it starts to fail could open the door to treating multiple diseases.
Q. What can we do to take care of our cleansing systems while research progresses?
A. There are several things that have proven to be useful for almost all aging pillars, many of which are interconnected. The first is nutrition. In the case of autophagy, an excess of fats is not helpful because it causes the cleansing systems to clog. "When there is too much fat, they cannot move through the cell and cannot clean properly." The same happens with excess sugars, which form a kind of branches on the surface of the systems that prevent them from advancing. Nutrition is essential for these systems because it is also key to activate the recycling function they carry out.
Q. When does recycling come into play?
A. The motivation to clean and recycle is related to nutrition. When your cells do not have the energy they need, they start looking around to "find something they can eliminate and break into pieces to obtain that energy." Imagine going to a house in the countryside and finding that the heating does not work but you have a fireplace. You will also look for things to burn and get warm, and you will not take the best table in the house to throw it into the fire, but rather some broken piece of furniture without legs. Cells do that every day. If you are not eating continuously, they have to find ways to get energy, which motivates them to look for damaged or malfunctioning things to reuse.
Q. Could this motivation be achieved through intermittent fasting?
A. We have seen that spacing out meals is quite important. This way, the cell has more motivation to clean and recycle. In this sense, it is more important to space out meals than the number of calories you consume. Once again, this timing should be personalized. Perhaps in some cases, it is appropriate to eat within an eight-hour period and then go 16 hours without eating, while in others, periods of 12 and 12 may be more effective. But in terms of cellular cleansing, we have experimentally seen that leaving that space is important, which "improves the cleansing system."
Q. What other factors influence?
A. Exercise is also very important. But I would highlight something very democratic before that, because everyone can do it and it costs no money: sleep. If you have a store, you do not start cleaning it when you have customers there, but when you close the shutter. Cells do the same. Restful sleep is essential for cellular cleansing. But we are ruining it by taking electronic devices to bed and staying up late working or watching TV. Additionally, there are two other factors that I did not expect but have also proven to be very important.
Q. What are they?
A. One of them is interpersonal relationships. Socializing, sharing time and positive interactions with other people, which is also very democratic and again free, is crucial. There is evidence that individuals who have been abused or have experienced stressful socioeconomic conditions or persecution have compromised autophagy. We have also seen in mouse models that experiencing bullying also affects cellular cleansing. The other aspect that we have seen to influence is having a positive attitude. In studies with centenarians that we are conducting, we have seen epidemiologically that it is a factor they share. They are people with a positive attitude, which is related to lower stress levels, a factor that is detrimental to cellular cleansing and aging, and also with higher levels of endorphins, which also favor many of the aging pillars, which as mentioned before, are interconnected.
"My mother always said that in a clean house, everything works better," recalls the scientist. "And we are seeing that it is really the same at the cellular level. When the cell can carry out cleansing, the mitochondria also work better and produce more energy because they are no longer swimming in garbage, for example. This interconnection gives us hope that we will not have to repair every aging pillar, but by acting on one, we will notice benefits in other areas," she points out.
The goal, she insists, is not to prolong life but to gain years of healthy life. "The ideal would be to live like centenarians," she concludes. More than 10 decades of healthy life and just a whisper of illness before passing away.