Fight against aging

Treatment of Aging

David Gems, Serious Science
Translation: Irina Lineva, Post-science

Aging is one of the main issues of biology and medicine. Scientists have learned by genetic, pharmacological and other methods to increase the life expectancy of model organisms with natural elasticity of aging processes. However, so far there is no reliable way to delay a person's old age. What are the problems facing researchers in the field of gerontology and how do dietary restrictions affect the aging process of the body?

Aging and age-related diseases

The fight against aging is a complex topic. First of all, I should say right away that I fully support the idea of fighting aging, because aging is terrible. It is a part of human existence, but it is impossible to accept it. I sometimes tell students: imagine that someone comes to you and says that in 20 years some people will break into your house in the middle of the night, kidnap you and torture you for two years until you die. This is what human aging looks like. This was the case with my parents: age-related diseases killed them before my eyes. Aging is a scary thing. 

As for the very idea of fighting aging, there is one problem here: it is not quite clear what we mean by this. We do not distinguish very well between aging and age-related diseases, although sometimes scientists make such distinctions. The fight against aging is also the fight against age–related diseases, but does this mean that coronary bypass surgery or hip replacement are anti-aging? Perhaps, usually it means something completely different. In addition, after some studies of C.elegans and other animals with a short lifespan, it seems as if there is one central mechanism of aging, however, in all likelihood, this is not the case. But if there is no central mechanism of aging that could be influenced, and if there is no difference between aging and age-related diseases, what can be considered a fight against aging? What does it mean? 

I would suggest as a solution to this problem to define the fight against aging as preventive therapy – partly to separate the treatment of aging and the treatment of any age-related diseases. Thus, this approach suggests preventing aging rather than treating it. It is based on the knowledge we have gained in laboratory experiments: according to research, we can interfere with physiological processes and prevent or at least slow down the development of age-related diseases. This is clearly seen in different animal models. 

Finding a Cure for old age

However, there are also problems associated with this definition. For example, any means that prevent at least one aspect of aging should already be considered as a cure for old age. For example, a sunscreen that protects the skin from the effects of ultraviolet radiation is in some sense a cure for old age, since it prevents skin aging. A visit to the dentist, who will remove plaque for you, within the framework of such a concept, can also be considered as a fight against aging. 

The idea of fighting aging in general, and not with its individual aspects, seems extremely interesting. If you edit individual genes in C.elegans, you can greatly increase their life expectancy – two, three, four times; one group was able to increase it tenfold. That's what attracts me to gerontology. It looks as if there are some fundamental processes underlying aging, and if we can understand them, we will achieve amazing results: we will be able to dramatically slow down aging and delay the development of age-related diseases for many decades. 

This approach correlates with some theories of aging that dominated in the 1990s, in particular with the theory of oxidative stress. Scientists believed that if you stimulate the recovery processes in the body, you can completely take control of the accumulation of damage and dramatically increase life expectancy. We thought that everything was moving in this direction, but recently it became clear that the higher you climb the evolutionary ladder – from worms to flies, mice, rhesus monkeys, humans - the less elastic the aging of the body. 

In the last few years, scientists have been shocked by the results of studies of dietary restrictions in rhesus monkeys. In rodents and many animals with low life expectancy, such restrictions significantly slow down aging: in rats and mice, as a result of experiments, life expectancy increased by 50%, the occurrence of a wide range of age-related diseases was suppressed. A similar study was conducted on rhesus monkeys, but here we were disappointed: most of the effects we noticed looked more like we just protected the animals from the harmful effects of overeating - we saw a completely different picture in rodents. 

I think it is now unlikely that we will find in humans some magical elastic aging processes like those that we noticed in C.elegans, and they can be corrected. However, in the field of gerontology, everything is changing rapidly, and this gives it a special charm in the eyes of those scientists who are engaged in it: everything is unstable here, theories arise quickly and disappear quickly. 

Senolytics

So, recently an incredible discovery was made in the field of the work of senescent cells in rodents. Senescent cells are a special type of cells that accumulate with age. It has been proven that they affect the development of a whole range of different age–related diseases - from various forms of cancer to cataracts, cardiovascular diseases and many others. These cells can be removed with the help of complex genetic interventions, as well as through a special class of drugs – senolytics.

Experiments on mice have shown that as a result of such an intervention, an amazing effect can be obtained, in fact, large-scale protection against age-related diseases: all these diseases still occur in mice, they just develop later. Thus, this type of intervention does not affect the aging process as a whole, but apparently affects the underlying cause of multimorbidity characteristic of elderly patients. These are very good results, and they are fundamentally different from the approach that conventional medicine adheres to – it approaches age–related diseases very simply: we will wait until a person develops this or that disease, and then we will study diseases separately within the framework of separate disciplines - oncology, cardiology, and so on. 

So the results of working with senescent cells are just fine, but they were obtained on mice. Personally, I think there are good prospects that this will work for people, but we have been through this many times. So I am not very optimistic: it is unlikely that we will find a medicine that will radically affect life expectancy with the technologies we have. But I think that, for example, those drugs that remove senescent cells look promising as an example of a treatment regimen that grew out of the experimental biology of aging. 

Problematic issues in the field of gerontology

I don't want to give the impression that I am pessimistic about the prospects of gerontology. I'm probably optimistic and pessimistic at the same time. A lot of discoveries initially looked extremely promising: plasticity in aging, which we observe in animals with a short lifespan; the theory of oxidative stress and the whole theory of aging as an accumulation of damage, which was supposed to provide a radical breakthrough; dietary restrictions that disappointed us, and the like. Apparently, humans do not have this natural elasticity of aging processes that we see in animals with a shorter lifespan, at least with respect to slowing down the aging process. 

This idea is also correlated with the recently established fact that the maximum life expectancy of people has been growing every year for many decades, but recently, around 2000, it reached a plateau. In addition, it became clear that information about some real long-lived record holders may be unreliable. For example, recently it was suggested that the super-long-lived Jeanne Kalman could actually be not Jeanne Kalman, but her daughter, who after her mother's death began to impersonate her.

But if you look on the other hand, we can say that people have elasticity of aging processes, it just works the other way around: these processes can be accelerated, and this happens, for example, if a person overeats. With obesity, apparently, the aging process accelerates. So there is a possibility that those interventions that protect animals from aging can be used to prevent accelerated aging in overweight people. 

But what really makes me optimistic is the potential to understand what aging is. It should be possible – another question is what we will do with this knowledge later. I think the basic concepts of aging have changed so much in recent years that we clearly have to get to the moment when we get the fundamental basis for understanding aging. This should give us an opportunity to understand what we can do to prevent age-related diseases and to ensure that people live longer in the future while maintaining good health.

About the author: David Gems – Professor of Biogerontology, University College London.

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