How to look for a pill for old age
An old age pill: myth or reality
Alpina non-fiction publishing house has published a book by biologist and scientific journalist Polina Loseva "Counterclockwise: What is aging and how to deal with it." In it, the author described in detail what specialists in the field of aging – gerontologists do, what results they have already been able to achieve, what can protect us from aging and whether it can be called a disease. "Snob" publishes one of the chapters.
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For the problem of living too long, which complicates our research on aging, we have already come up with several solutions – you can investigate extreme cases or focus on the aging rate of specific people. But the difficulties do not end there.
There are no two identical living organisms in nature. Even the two cells that resulted from symmetrical division differ from each other in many parameters. What can we say about people then! And if we want to find out how our pill affects biological age, we must first make sure that no other factors will affect it during the experiment. But aging is a multifaceted process, and it is not always clear which parameters we need to control. If you can still put mice in a cage and create exactly the same living conditions for them, then you can't do that to people. Each of the subjects will live his own life, unlike the life of a neighbor, and then go understand what exactly helped or prevented him from prolonging this life.
The most revealing experiments on people so far have been staged by history. A classic example here is another study related to starvation, where the First World War acted as an experimenter, and the participants were residents of Copenhagen who suffered from interruptions in the supply of food. After the war, the government food adviser estimated that people died a third less often during the war than in pre-war peacetime.
It would seem that nature throws us the finished results of the experiment. But should we trust them? A lot of factors could have intervened in this situation, which no one took into account. For example, residents of the city could experience – and certainly experienced – increased psychological stress. Or, among the people who stayed in the city during the war, there were more women who, on average, live longer than men. Or maybe it's not about calorie restriction at all, but about changing the ratio of some foods in the diet.
It turns out that the older the study, the longer it lasts and the more benefit it could potentially bring to us. However, the earlier it started, the further it is from the standards of clinical trials and the less chance we have to check its quality.
The third difficulty in experimenting with people may seem frivolous at first, but sometimes it is she who greatly lets researchers down. These are the whims of the subjects.
A clear example of how human nature triumphs over the idea of an experiment is the CALERIE project, the purpose of which was an attempt to study how calorie restriction affects people in real time. A few years ago, within the framework of this project, scientists launched another clinical study: they selected volunteers with a slight excess weight and painted individual nutrition programs for them. For two years, the participants of the experiment had to limit their diet to 75% of the amount of daily energy consumption. At the same time, researchers regularly measured different markers of their biological age, trying to track changes over a short period of time.
But the carefully planned experiment ran into unforeseen problems. As one of the project managers complained at a recent conference, "the subjects refuse to eat so little." In two years, they reduced the caloric content of their diet by only 12% instead of the required 25%, that is, they overcame only half of the necessary restrictions. And despite the fact that the results of the experiment turned out to be rather positive – people did not experience serious side effects, but their risk of cardiovascular diseases decreased - the researchers still did not achieve their goal. And they are hardly able to change this: controlling all the subjects' meals and stopping their attempts to eat something else in between breakfast and lunch is an impossible task.
Taking into account all the nuances that make experiments with people almost impossible, it seems surprising that someone still conducts them. However, to do this, scientists have to carefully disguise aging research under real medical tests: that is, to test their hypotheses about the effectiveness of pills for old age on the example of specific diseases.
To begin with, you need to choose some real symptom - it would be good if it was somehow related to age, for example, inflammation of the joints, atrophy of the thymus (the gland that produces part of the immune cells) or diabetes.
Then you need to choose a type of treatment that could become a "pill for old age" and at the same time ease the course of the disease. For example, senolytics – drugs that kill old cells - are now being tested in this way. And old cells cause many pathological processes, such as those that accompany diabetes mellitus. Therefore, senolytics are aimed at two birds with one stone: a small one – diabetes, and a large one – aging in general.
Next, you will need to find volunteers and collect the maximum amount of data about them, so that later you can exclude the impact of their health and lifestyle on its duration. And in the course of treatment, you will have to monitor not only the course of the target disease itself, but also the markers of biological age in order to detect an early influence on the aging process. For example, recently a group of scientists conducted a study on the restoration of the thymus and quite unexpectedly discovered that the subjects were younger (biologically) for a couple of years.
And finally, at the end of the study, it would be good not to lose sight of the subjects, so as not to miss the long–term consequences of treatment - what if they really live longer, as participants in the Minnesota experiment?
This strategy looks like a win-win. If the pilot studies are successful, then at least we will have a way to protect the elderly from diabetes and joint inflammation. At the same time, we will get data on how the patients' body reacts to these medications, whether there are side effects from them and what is their safe dose. And a little later we will see how the life expectancy of the participants in these studies has changed.
And even if the initial experiment pursued other goals (as in the case of the Minnesota experiment), by the time we are (if we are) ready to conduct real research on real pills for old age, we will be able to rely on the results of previous studies. This means it will be easier to get permission from the ethics committees, convince investors and attract participants.
Thus, despite all the obstacles that we put ourselves on the way to prolonging life, we still have an idea how to get around them. However, even with the help of this cunning plan, the development of pills for old age will take at least decades – which, of course, is less than the 120 years we talked about at the beginning of the chapter, but more than many researchers and investors can afford.
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