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Coral Sanfeliu, aging researcher: ‘Sitting eight hours a day affects brain connections’

The scientist has just published a book on the positive effects of exercise on brain health and the genetic mechanisms that are activated in response to physical activity

Coral Sanfeliu
Coral Sanfeliu, director of the Neurodegeneration and Aging Group of the Barcelona Biomedical Research Institute.Gianluca Battista

Coral Sanfeliu, 69, directs the Neurodegeneration and Aging Group of the Barcelona Biomedical Research Institute. In her career, she has focused on studying what happens to the brain with aging and how exercise can prevent the deterioration brought on by age. Sanfeliu has just published The Brain in Motion together with José Luis Trejo, director of the Lifestyle and Cognition Group at the Cajal Institute in Madrid. In just over a hundred pages, the two researchers offer the main findings on how exercise can help the brain and healthy aging.

Question. One of the terms you bring up in the book is the benefit of hormesis, how the slight harm to the body that exercise can cause has a long-term benefit. But the harm, too, can be excessive. What is the correct dose of exercise?

Answer. Of course, if the damage is very severe, this hormesis will not occur. It is a term that can also be applied to other problems, resistance to an upset or trauma, which you then create defenses against that stress. But if the stress is excessive, the damage will be much greater than the possible benefit.

In the case of exercise and its effects on the brain, there are studies in humans, but the main ones are in mice. We have seen, for example, that there are epigenetic changes, which are like labels that are placed on genes, which activate genes against inflammation anda oxidative stress. So, you may have an injury, for these reasons, and you are already ready to overcome it, because certain networks in the brain are reinforced or more networks are generated. It is not that the damage will be avoided, but that there will be better overcome when it happens. That is resilience, in this case induced by a hormetic response.

Q. Many people start exercising after many years of inactivity and do not start off with mild exercise, but rather with training for half-marathons or crossfit. Is this a good idea?

A. It depends. Science is not black and white. Sport is good and has many advantages, but it has to be progressive. The hormesis level gets better and better and the threshold at which an exercise can be harmful gets higher and higher. Regarding the effects on the brain, this does not mean that athletes are smarter than others. If you do a lot of exercise, you are not going to be smarter, although you will have optimized brain responses. However, if you train very hard, if you do marathons, you have to monitor your heart rate, your vital signs, do tests. But from the brain’s point of view, strenuous exercise is not going to benefit you.

Q. Are the benefits the same if you start at any age, or do you need to start early?

A. What we have to think about is not that exercise improves our health, but that if we don’t do it, our health worsens. Children have to move, their brain is developing, and they have to interact with the environment. In this training, exercise is important. If they don’t like one sport, they have to look for another, or go somewhere to dance, but they have to move so that their brain properly matures. And for older people, any time is a good time to start.

Q. Can cognitive impairment be repaired if you start playing sports at a very advanced age?

A. What has been damaged for so many years will not be repaired. Exercise cannot fix us if there is neuronal death or a significant loss of connections. But in normal aging, when there is no neuronal death or additional pathology, it will protect us. If we are talking about pre-Alzheimer’s or pre-dementia it is very difficult, although there are studies that have shown that some damage can be reversed. Neither exercise nor diet will cure dementia, although its progression could be somewhat delayed.

Q. What is the minimum amount of exercise needed to see a benefit?

A. It all adds up, but it has to be an activity with a certain intensity. If we walk to work, it can’t be a stroll while looking in shop windows, we have to walk as if we missed the bus. And it has to be for at least 10 minutes at a time, so that there is time for the heart rate to accelerate, factors to be released and everything to be activated. And you have to do a weekly minimum. One recommendation is 150 minutes, which is recommended by the WHO.

Coral Sanfeliu
Coral Sanfeliu, researcher and author of 'The Brain in Motion'Gianluca Battista

Q. There is also talk of the damage caused by sitting for too long, something that in our society is necessary in many jobs.

A. Sitting eight hours a day is harmful and affects brain connections and neurotransmitters. It is true that sitting in front of the computer is not the same as sitting in front of the television, which is even worse. When we spend eight hours sitting, we have to do an hour of activity to compensate. Sedentary lifestyle increased with the pandemic, and it is feared that dementia will increase, not only due to the long-term damage that the disease may have, but also due to inactivity. Apart from the rise in problems such as depression or anxiety.

Q. In your book, you say that the benefits of exercise are not only for those who practice it, but also for their descendants.

A. This has been studied by authors such as José Luis Trejo, co-author of the book, who found that mice that exercised, mated with females that did not exercise, produced offspring that, although they did not exercise, had mitochondria with better functionality and more beneficial brain changes than the offspring of parents who did not exercise. As a mechanism, it was seen that there was an epigenetic factor called microRNA that was transmitted with the sperm and reached the embryo, although it is likely that there are other ways in which this intergenerational transmission occurs.

Q. Does it make sense to consider the possibility of creating pharmacological treatments to replace the effects of exercise on the brain, for people who cannot or do not want to exercise?

A. Yes, it makes sense. If we identify mechanisms by which exercise activates antioxidant genes or protects against inflammation, or releases factors that are going to benefit neurons or neurotransmitters, we can look for treatments that activate those pathways that go from the gene to the production of a beneficial protein. Sirtuin, for example, is a protein that reduces oxidative stress in cells, and its production is activated by exercise. It is a survival and longevity enzyme, and we are studying substances that activate the gene that produces it: one example is resveratrol, which is in grapes. Other options are those that seek to control inflammatory processes, which deteriorate with age and have negative effects on the brain.

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