About the latest developments in the biology of aging and the most affordable way to extend life – in a conversation with a visiting scientist at the Buck Institute for Research on Aging and an employee of the Formic Ventures fund Maria Konovalenko
How do you define aging?
– There is no concept that would unambiguously describe this phenomenon. Leading scientists have not yet reached a consensus on this issue, the answer to it lies in the philosophical and, I would say, epistemological plane. At the moment, there is no scientific paradigm describing why we age. In 2013, however, an article was published that describes the nine main mechanisms of aging, but they are not very isolated, many of them intersect.
– Tell us what research you are doing now.
— This year, I received my PhD degree from the joint program of the University of Southern California and the Buck Institute, specializing in Biology of Aging. My work was aimed at investigating the following question: how strongly do the two mechanisms of aging intersect – the accumulation of senescent (aging. – Trends) cells and dysregulation of the mTOR pathway. A few words about mTOR, this is important.
Imagine a cell. She at some point begins to divide and gives two daughter cells. In order for division to occur normally, the cell must have enough nutrients to duplicate DNA, produce a large number of proteins and everything necessary. In order to understand whether there are enough nutrients, there are sensors in the cells, and the mTOR protein is one of the main ones: it reacts to the available amount of glucose and amino acids and, depending on this information, regulates the synthesis of various biomolecules. In other words, if a cell has the building blocks, it will start producing and dividing. If there are not enough building blocks, for example, when there is little food, then mTOR becomes inactive, and the cell literally switches to the mode of getting rid of accumulated broken proteins and intracellular debris, and, accordingly, the synthesis of production is paused.
This idea is actually fundamental. Scientists have noticed that substances that inhibit mTOR activity lead to life extension.
Rapamycin is one of the few substances that, when taken by model animals, not only prolonged their life, but also made them healthier in many ways. Rapamycin is quite effective at inhibiting mTOR.
However, taking it as an anti-aging drug is dangerous because it has many side effects, from mouth ulcers to metabolic effects. It is registered in doses in which it is used as an immunosuppressant (drug for artificial suppression of immunity. — Trends) for people with transplanted organs. We do not yet know what dose is suitable for slowing down aging and in what mode it should be used. It remains to be seen, we just need clinical data.
– If we turn to the practical side of research, then what might the means for radical life extension look like: are these pills that will need to be taken every day for life or a single injection?
“I don’t think it will be one remedy. There are different mechanisms of aging, and interventions in them are also quite different. Therapy will not be designed to prolong life, but to combat some specific age-related disease. For example, with chronic renal failure, pulmonary emphysema, atherosclerosis, autoimmune and neurodegenerative diseases. We cannot randomly give people powerful drugs and hope for a “maybe”. People will receive these drugs under medical supervision.
– That is, they will begin to treat at a fairly mature age, when specific diseases already appear?
– Most likely it will be so with the first drugs. But, again, there are different possibilities. resTORbio, for example, planned to use mTOR inhibitors to improve immune function in the elderly. The subjects were given drugs, and then they were vaccinated against the flu and looked at the incidence, whether there was an immune response of the body. That is, for the use of this remedy, it is not necessary to get sick with something in order to receive treatment, the drug will need to be used preventively to improve immune function. Another company, Unity Biotechnology, is developing a drug against age-related eye diseases. In this case, you must initially have a specific diagnosis (diabetic macular edema), because a local injection is made.
— What other studies conducted in recent years do you consider promising?
– If we compare, say, what happened in the industry 10-15 years ago with what we have now, it will be “heaven and earth.” Interesting work comes out all the time.
For example, one of the best ways to prolong life and improve health is, of course, physical activity. There is a mass of literature on the positive impact of sports on human health and life. Recently, an article was published in the journal Science, the idea of which can be briefly described by the expression “exercise in a pill.” They compared mice that received exercise with those that did not. They were able to identify a protein that plays a big role in improving cognitive performance in exercising mice. Later, they were able to increase the synthesis of this protein in ordinary old mice, which eventually rejuvenated their brains and made them smarter. This is incredibly cool and promising, for example, for people who, for some physical reason, cannot go in for sports, but would like to get the effect of a sports load.
One more example. The blood-brain barrier is known to hinder drug delivery to the brain. In the laboratory of Professor Tony Wyss-Korea at Stanford, they proved that in fact, the surprisingly active transport of proteins in a young organism is carried out at the expense of receptors. But in the course of aging, the efficiency of this “transport” decreases, and, roughly speaking, “whatever” gets into the brain of an elderly person. It seems to me that this observation may lead to a change in the approach to the fight against neurodegenerative diseases.
Another example. As I said, there are nine mechanisms of aging. Scientists at the Buck Institute created two mutations in the worm. One was in the insulin receptor, and the other was inside the mTOR signaling, one of the participants in the signaling pathway was modified. So, if you form only the first mutation separately, the worm will live 60% longer, and if the second – 100% longer. And if you provoke both mutations at the same time, the worm will live not by 160%, but by 450% more! More recently, scientists have identified the mechanisms responsible for this powerful life-prolonging effect. So far, this knowledge has not yet been translated into clinical trials, but it is not difficult to imagine that such attempts will be made in the near future by one of the many new start-ups in the field of longevity.
How does diet affect life expectancy?
“Diet is incredible. This was first demonstrated in the mid-1930s of the last century. The underlying idea is that cells have sensors that respond to the amount of nutrients and that regulate anabolism and catabolism, production and processing. If you reduce the number of calories consumed by the body, then a living organism can live 30-40% longer, depending on the body and how much the calorie content of food is reduced. There are other examples such as the ketogenic diet (a diet high in fat and low in carbs. — Trends), intermittent fasting, a connection with circadian rhythms has also been found, that is, when we eat plays a big role, etc. For the most part, fitness gurus don’t base their recommendations on clinical data, and few diets pass the test. But, for example, the diet of biologist Walter Longo is one of the few exceptions. His trials on humans have shown that in addition to weight loss, there is a decrease in c-reactive protein in the blood, that is, it also has an anti-inflammatory effect.
– Some believe that the ultimate goal of such research is the victory over aging or immortality. Do you think this is a blessing for a person or a heavy burden?
– The research that is being carried out now has little to do with immortality. The task of scientists is to understand the mechanisms of aging and make a person healthier. Life extension will be a side effect. Nobody wants to prolong sickness and suffering.
All interventions aimed at increasing life expectancy will make a person smarter, his organs will work better. We will fight cancer more effectively, the likelihood of getting sick with some kind of age-dependent disease will decrease. But now, unfortunately, it is impossible to somehow radically extend your life.
If for a moment we imagine such a fantastic situation where immortality is possible, we can say that it will be very cool. People will have more time for all the things they like, it would be possible to travel to distant planets. If a long life becomes a burden for someone, they will be able not to use technologies that prolong it.
— How do you feel about biohacking?
– Rather negatively, now there is a lot of hype around this word. For me, biohackers are people who use various practices and means on themselves that can greatly harm them, and incite others to do the same. For example, they uncontrollably inject themselves with drugs for gene therapy. All drugs and methods used by people must be safe and tested.
What else do you do to keep yourself healthy?
Doing sports. Over the past few years, I have increased the average number of workouts to five per week – these are strength and aerobic loads. I regularly take tests and do check-ups (comprehensive express examinations. — Trends).
– You are included in the Forbes Top 50 Women Futurists list. But in other ratings, mostly (or only) men appear. Why do you think male futurists are more famous?
– I have, perhaps, an amateurish view, but I think that the reason is that in many cultures girls are not expected from childhood to receive education in the field of STEM (Science, Technology, Engineering and Math, from English. Science, Technology, Engineering and Mathematics. — Trends). Society in many ways encourages a different career path. This, of course, must be fought. It is necessary to infect as many girls as possible with enthusiasm, because biologically women are no different from men and are able to occupy leading positions in any industry.
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