06 November 2019

On a mouse model

Life in the stuffiness has likened a laboratory mouse to a naked digger

Polina Loseva, N+1

Scientists have created a model that simulates the living conditions of a naked digger – a closed cage where the concentrations of oxygen and carbon dioxide are approximately the same. After being in such a cage, the metabolism of mice became closer to the naked digger: body temperature dropped, the amount of absorbed food and inhaled oxygen decreased. At the same time, the animals did not experience stress, and their wounds began to heal even faster than under normal conditions. The work was published in the journal Biogerontology (Tolstun et al., Metabolic remodelling of mice by hypoxic-hypercapnic environment: imitating the naked mole-rat).

The naked digger is known not only for its unique lifespan (more than 30 years, which is ten times higher than that of an ordinary mouse), but also for the fact that many signs of old age bypass it: it rarely suffers from diseases that are characteristic of elderly rodents, and its reproductive abilities practically do not decrease with age.

What exactly makes the digger resistant to most age-related changes is still not known. Perhaps one of the keys lies in its habitat: diggers live in cool underground tunnels – which is probably why their body temperature is lower than that of other rodents. In addition, the tunnels are poorly ventilated, and the oxygen content in them can decrease from the usual 20 percent to 10, and the amount of carbon dioxide, on the contrary, increase to 10 percent instead of tenths and hundredths of a percent.

Denis Tolstun from the State Institute of Gerontology in Kiev and his colleagues from Ukraine and Israel decided to test how such living conditions will affect ordinary laboratory mice. To do this, they took three groups of animals: young (3-4 months), adults (12-16 months) and elderly (24-26 months) and conducted two types of experiments with them. One corresponded to acute hypoxia – the animals were kept for several hours in a vessel with a closed lid, the other imitated chronic hypoxia: the animals spent three months in a cage, the oxygen and carbon dioxide content in which was maintained at 10 percent.

In an experiment with acute hypoxia, the researchers found that the amount of oxygen that mice consume per unit of time fell three times, as well as the amount of carbon dioxide exhaled. From these data, scientists concluded that the metabolism in the body of animals slowed down. In addition, the surface temperature of the mice's body dropped by fractions of a degree in three hours – both in young and elderly animals.

Being in a stuffy cage for a long time also affected the mice equally regardless of their age. The amount of absorbed and exhaled gases decreased by half in the first ten days, and then it reached a plateau and remained unchanged. The body temperature also dropped by a few degrees, and then stabilized at this level.

In stuffy conditions, the animals began to eat 40-50 percent less than usual, although they were provided with plenty of food, and lost 25-30 percent of their body weight. At the same time, the mice did not experience constant stress – at least at the cellular level. The amount of heat shock proteins that accompany intracellular stress remained unchanged, despite living in stuffiness. From the point of view of behavior, the researchers also did not notice any changes – neither in the level of activity of the mice, nor in the amount of sleep.

To test how much physiological processes in the body of mice suffer from a lack of oxygen, the researchers inflicted wounds on their skin. However, the healing of wounds in hypoxia took no longer than usual, but, on the contrary, a few days less.

Thus, under the influence of stuffiness, the metabolism in the body of mice was rebuilt and began to resemble a naked digger more: body temperature and oxygen absorption decreased, without inhibiting the basic physiological processes. However, it is still unclear whether this explains the longevity of the diggers – some scientists believe that it is not the speed of the metabolism itself, but the speed of disposal of its toxic by-products.

Nevertheless, the authors of the work believe that their method has another important plus: it can be used not only on animals, but also on humans to simulate calorie restriction. Under conditions of hypoxia, mice consumed less food, but they did it evenly, without periods of fasting and overeating, without showing signs of stress – which means that one can imagine that this will one day become a convenient way for people to follow a diet.

It used to be believed that naked diggers are not susceptible to senile diseases at all, but this statement has been refuted many times. First, they were found to have tumors, and then they found out that individual cells in their body were still aging. But naked diggers have found another superpower – to survive in oxygen-free conditions, in an atmosphere of pure nitrogen.

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