restricting oxygen lengthens life in mammals

At the end of the 1970s, a group of scientists published in the ‘International Journal of Biometeorology’ a curious study in which they compared the health of two detachments of the Indian army: the first, made up of 130,700 men, settled between the years 1965 and 1972 in the plains, at 760 meters above sea level; the second, made up of 20,000 soldiers, was assigned at the same time to the mountains, at an altitude of between 3,692 and 5,538 meters.

After comparing the health data of both groups, the researchers realized that diseases related to aging, such as diabetes, hypertension or heart disease, were much lower in the ‘high mountain’ group; as did the overall morbidity rate, which stayed low while soldiers stationed at lower altitudes fluctuated up and down. Is it likely, then, that living at higher altitudes can lengthen our lives?

Science has proven that this is the case for some species of yeast, worms and flies, for which the reduction of oxygen retards their aging and, therefore, their death. It’s also long been known that the nondescript (and nearly indestructible) naked mole-rat lives peacefully in hypoxic burrows (in fact, they need carbon dioxide almost more than oxygen). Now, a group of scientists from the Massachusetts General Hospital in Boston (USA), add laboratory mice to the list, for whom the deprivation of this gas meant a life twice as long. The results have just been published in the journal ‘PLOS Biology’.

In search of the ‘anti-aging’ recipe

Scientists focus their efforts on researching how to prolong life, above all, healthy. At the moment, several chemical compounds have been identified and caloric restriction (fasting) is indicated as the most promising habit when it comes to extending our life. However, oxygen deprivation, which has given such good results for other species, has never been investigated in mammals. Neither in humans: there is not much literature on the matter beyond the study of the seventies on the comparison of the battalions of the Indian army.

To test its potential, the team, led by Robert Rogers, set out to carry out experiments on laboratory mice. But not with just any: genetically modified specimens that instead of surviving more than three years, like normal mice, end their life cycle in six months. “We chose an accelerated aging mouse model because it has a shorter lifespan, accumulates the physiological and biochemical signs of aging in less time, and we know it responds very well to caloric restriction, the most common way organisms live longer. », explains Rogers to ABC.

After weaning the mice at four weeks, some of the modified mice were placed in a hypoxia chamber that simulated the same environment that exists at Everest Base Camp at 5,000 meters: oxygen from ambient air, which normally registers 21 percent oxygen, is reduced to 11 percent.

The mice lived under these conditions until their death. By comparing the data, the researchers found that the hypoxia chamber specimens had a doubled lifespan (an average of 23.6 weeks to live versus 15.7 for genetically modified mice living under normal oxygen conditions). Not only that: in the oxygen-restricted mice, age-related neurological decline was also delayed. “We’ve been excited for a long time that hypoxia could be beneficial in a model of aging,” Rogers says, “but we weren’t so sure it actually worked.”

A different mechanism than caloric restriction

The experiment did not end at that point. Previous research has shown that caloric restriction—basically, reducing food intake—extends life in many animals, including rapidly aging mice like the ones in this study. The authors then wondered if the oxygen restriction prolonged their lives simply because they, due to these simulated ‘high mountain’ conditions, ate less.

“We found that hypoxia did not cause these mice to eat less or weigh less than normal, so we think oxygen restriction is acting through new mechanisms, not simply inducing caloric restriction,” Rogers says. That is, there is an alternative route, different from caloric restriction, by which the mice lived longer.

Extrapolate the results to humans

The authors note that these findings support the hypothesis that living with less oxygen is a potential ‘anti-aging recipe’ for mammals, perhaps including ourselves. “But it is too early to speculate on the implications of these results for human aging,” says Rogers.

The main criticisms of the study come from the class of mice used for the experiment. “This study is a very interesting proof of concept,” says Cayetano von Kobbe, Senior Scientist at the CSIC and researcher at the Severo Ochoa Molecular Biology Center, for SMC Spain. (…) The mouse model of premature aging used is very specific, which limits the conclusions. Ideally, it would be compared to the effect of low oxygen levels in normal mice, although that would imply trials lasting more than two years, and not six months, like those of the present study.”

For his part, Nabil Djouder, head of the Growth Factors, Nutrients and Cancer Group at the National Cancer Research Center (CNIO), explains to the same platform that “this finding may have implications for the development of therapies aimed at aging and age-related diseases in humans. “For example, living in conditions with restricted oxygen levels, such as at high altitude or in mountainous areas, could prolong life expectancy,” says Djouder, who stresses, however, that more studies are needed to verify this hypothesis.

Also, he argues, one should study the consequences of ongoing chronic hypoxia (ie, living in low-oxygen conditions, not just a temporary reduction) or study how exercise can to some extent lead to this phenomenon. “If future studies confirm the findings and demonstrate their applicability in humans, potential applications could involve the development of interventions that simulate or mimic ongoing chronic hypoxia in a controlled manner,” she concludes.

By Editor

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