Salvador Aznar Benitah has a degree in Molecular Biology and Biochemistry from McGill University (Montreal, Canada) and a doctorate in Molecular Oncology from the Biomedical Research Institute of Madrid. He was a postdoctoral fellow at the London Research Institute (Cancer Research UK), where he studied the behavior of adult stem cells, and in 2007 he established his own laboratory at the Barcelona Center for Genomic Regulation as an ICREA researcher. For more than 10 years he has been a group leader at the Barcelona Biomedical Research Institute.
One of the central topics of Aznar’s department is the effect of circadian rhythms on aging, and conversely, how the passage of years affects our internal clock. A vicious—and negative—circle that we can try to stop with our lifestyle. The times at which we eat, for example, may be a key factor, according to the latest research. He tells us about it himself from Canada, during one of his stays to investigate.
They study the relationship between circadian rhythms and aging, what have they found?
We see how the circadian rhythm or biological clock affects daily functions and how, unfortunately, we lose the robustness of that clock as we age. This is a cause and consequence of aging. We study why we lose the ability to keep our clock properly aligned and what the effects of this are.
Why does the biological clock deteriorate with age?
This is the million dollar question, but we don’t know. What we first did was characterize what the function is when the body is young and works well and we saw that all or almost all of the functions that our tissues and organs have to perform are subject to the circadian rhythm. Evolutionarily, this helps preserve tissue and increase longevity.
It says that the body’s clock does not respond to external factors, but rather internal factors of the body itself. How is this?
We do not fall asleep because it is going to get dark, nor do we wake up because it is daylight. The biological clock is not a response to the outside, but rather it tells you that, as night is coming, you are going to sleep, and as the sun is going to begin to rise, you begin to wake up. The clock prepares the body for what is to come. This happens at all levels, your brain, your liver, your digestive system, your respiratory system awakens…
Does it mean that if we are locked in a dark room we continue to wake up when the sun rises outside, even without having contact with the outside or the light?
Exact. If we were locked up for a month, we would continue to fall asleep at night and wake up when it was daylight outside, it is our internal clock that rules. If this were not the case, jet lag would not exist, and we would sleep without problems when it is night. Our skin is another example: in the morning it prepares the melanocytes (which makes us tan), because it knows that soon we will be exposed to ultraviolet light from the sun. It protects us from the damage of that light. If the watch stops working well, the skin has no protection, and the ultraviolet light will do more damage.
Does this watch protect us from aging?
Indeed, it is a fascinating machinery, it seems that someone has programmed it. The biological clock, while protecting skin cells from ultraviolet light, tells those cells “now is not the time to divide, protect yourself” and when there is no ultraviolet light, the clock tells them “now it’s time to divide.” “You can split up and repair whatever damage you have.” As we lose this biological clock, we age… and when we age, we lose that clock. It’s like a fish biting its tail! You lose the clock because you are accumulating more damage, and since you are accumulating more damage, you age more and this affects the clock. A vicious circle!
In addition to this effect on the skin, what other aging consequences occur as a result of this?
As we get older, the sleep cycle changes, the hunger cycle changes… You eat when you wouldn’t have to according to the pattern you have had throughout your life, for example. All functions that depend on this circadian machinery show elements of arrhythmia in old age.
What functions, besides sleep or food intake, are powered by circadian rhythms?
There are hundreds of them in the skin, in the liver, in the heart, in the muscle, in the intestine… Each tissue has to have its own clock because it has particular functions. Wakefulness, activity or inactivity, when you eat or not, the ability to metabolize food well, are functions regulated by circadian rhythms. If you wake up at three in the morning and try to eat a steak or some lentils with chorizo, 99% of people will feel bad. On the other hand, eight hours later, it will feel good to them, in the same body and the same organs. The time we eat is very important, and with age there are foods that taste worse because the biological clock begins to not work well.
Can we do something to keep the biological clock more steady?
The evidence we are beginning to have is a partial “yes.” For example, we know that the cafeteria diet, the high-fat diet, accelerates clock dysregulation, and therefore aging. You start to see changes in the clock at age 50, instead of at 60 or 70, it speeds up a lot. On the other hand, if you maintain a low-calorie diet, with few calories, little saturated fat and little sugar, this lengthens the period in which the biological clock works well. Food restriction over time is also effective, such as a daily fasting period, eating dinner early and going between 12 and 14 hours without eating. The effect will be seen quickly in certain parameters, in approximately one month, but for a long-term benefit in aging to be maintained, it has to be a maintained habit.
What is the most suitable diet to age in the best possible way?
Without too many saturated fats and with a lot of common sense. We all know that a healthy diet consists of vegetables, fruits, nuts, meat in moderation, oily fish for its omega-3, and the less processed food and bad fried foods, the better. You don’t have to reinvent anything, you don’t have to eat quinoa. And if you eat a plate of lentils with chorizo ??one day, nothing happens. If you do it in moderation, time is set to deal with those fats. Now, if you eat chorizo ??and bacon every day, you know what you are exposing yourself to.
But they have done studies on the time windows of intake, and they are also determining factors, almost as much as the type of diet!
There are interesting experiments that compare what happens if cafeteria food is eaten at any time, or a time restriction is imposed. In mice, eating the same calories and amount of fat, with temporary restriction, they practically do not gain weight. And this can be applied to humans, so we know that when we eat is just as important as what we eat. If you have a healthy diet, but eat it at the wrong time, it can have harmful effects on aging. Maintaining hourly intake schedules and limitations is allowing our clock to perform the function for which it was set, after millions of years of evolution. There are times when it is good to do something, and others when it is not. It’s not good to sleep during the day, your body doesn’t understand it; Your body tells you to sleep at night, which is when it’s your turn.
He said that the effect of calorie restriction for 12 or 14 hours will be seen quickly in some parameters. Which is it?
Blood pressure, cholesterol levels, glucose levels, muscle capacity to recover from exercise, heart capacity… You are more predisposed to being healthier. And we have seen in research that, although exercising is always positive, it has more benefits if it is done in the afternoon. If you can’t, it’s better to do it in the morning, but if you can choose, in the afternoon it is much more beneficial, more or less between six and eight in the afternoon.
The reason?
Because the clock of the heart and muscles, and their communication with other tissues, their coupling of functions, the muscle and liver or muscle and adipose tissue are better aligned at that time than in the morning.
If we keep the daily rhythms of sleep, wakefulness, meals, activity very stable and firm… will this make us age better?
The clock is disturbed with aging. But if throughout your life you do not keep your schedules and biological rhythms firm, you will accelerate this disturbance, the loss of the biological clock associated with age.
Taking shifts at work and changing schedules every week, to what extent does it age us?
The problem is in people who have very changing schedules, health workers, pilots or airline personnel, factory workers… Mouse models confirm that changes in sleep and meal schedules generate more predisposition, metabolic problems, a higher incidence of breast cancer. breast and prostate, greater risk of heart attacks and strokes… But there are few people who maintain that rhythm of schedules for many years because it is unnatural, it cannot be maintained. If you work at night you will probably get hungry at night, and if you eat a snack from the vending machine at three in the morning your body is much less prepared to digest those bad fats at that time, rather than at noon. This causes more damage to accumulate in the body.
All these findings on circadian rhythms and age have already been published. What practical application do they have in anti-aging medicine? For what purpose are your department’s investigations carried out?
The circadian rhythm and its functions are altered during aging. This prevents our organs from doing their job when it is time to do it and also loses synchronization between organs that have to work in a coordinated manner (such as those of the digestive tract). It would be very interesting to be able to identify therapies that keep our clock working properly and synchronized. However, before we could develop these therapies we had to understand how exactly the clock is altered during aging. We now know that the molecular machinery responsible for setting and maintaining the clock is not actually affected during aging, but rather it is the synchronization of clocks between different organs that changes most significantly as we get older. So now it’s about finding ways to maintain that synchronization. Studies in different animal research models show that if we keep the clock well synchronized, this allows us to delay many of the problems associated with aging. Therefore, we believe that these new therapies could be useful in the treatment of these pathologies.
