Oxygen reduction increases life expectancy in mice

Throughout the world, many research groups are working to unlock the secrets of longevity, to find out how aging and related diseases can be influenced.

This search has already uncovered some clues that may be key. For example, some factors, such as eating a low-calorie diet, have been shown to be generally associated with longer life expectancy.

In cellular studies and in animal models, such as the fruit fly or nematodes, oxygen restriction had also been associated with longer life span, although there were no data on its effects in mammals.

A new study published in the journal PLOS Biology changes that picture and provides, for the first time, the impact of limiting oxygen availability in mammals.. According to their data, in laboratory mice, oxygen restriction is also associated with a longer life expectancy.

Specifically, they have shown that submitting to oxygen restriction similar to that which would occur at 5,000 meters of altitude increases life expectancy by up to 50% and decreases neurological deterioration in these animals.

Led by Robert Rogers, from the Massachusetts General Hospital in Boston (USA), these scientists carried out different experiments on genetically modified mice so that they experience premature aging. By comparing the life expectancy of mice exposed to different levels of oxygen, the researchers found that those living in an environment with oxygen availability similar to what they would have at an altitude of 5,000 meters lived 50% longer than those without any oxygen. type of hypoxia or oxygen restriction. Thus, the average age of the former exceeded 23.6 weeks, while the latter was 15.7 weeks on average.

Furthermore, that oxygen restriction was also associated with a delay in the development of age-associated neurological problems.. In their work, the scientists point out the potential of their findings, although they acknowledge that more work is needed before knowing its impact on humans and the mechanisms involved in this relationship.

“Results that are difficult to extrapolate to humans”

“We found that continuous chronic hypoxia (11% oxygen, equivalent to what they would experience at Everest Base Camp) prolongs life by 50% and delays the onset of neurological problems in a mouse model of aging.” indicated, in a statement, Rogers. “While caloric restriction is the most effective and well-studied intervention for increasing life expectancy and health, this is the first time that oxygen restriction has been shown to be beneficial in a mammalian model of aging.” .

“This study is a very interesting proof of concept on the effect of low oxygen levels on the longevity of mice, demonstrating what had already been seen in other experimental models”, Cayetano von Kobbe, tenured scientist at the CSIC and researcher at the Severo Ochoa Center for Molecular Biology.

For Kobbe, “the mouse model of premature aging used is very specific (mutation of a gene involved in DNA repair), which limits the conclusions. The ideal would be to compare it with the effect of low oxygen levels in wild type or normal mice, although this would imply trials lasting more than two years, and not six months, like those of the present study.. Therefore, the results are difficult to extrapolate to people, firstly because of the obvious differences between mice and humans, but even more so, due to the fact that a mouse model with a very specific mutation was used.”

For his part, Nabil Djouder, head of the Growth Factors, Nutrients and Cancer Group at the National Cancer Research Center (CNIO), stressed that “this study is significant because it shows for the first time that “oxygen restriction” can prolong the life in a mammalian model of aging. It also contributes to our understanding of the impact of low oxygen levels on mammalian organisms.. However, the exact mechanisms through which hypoxia exerts its effects have yet to be determined.. Surprisingly, hypoxia did not significantly affect food intake and had minimal impact on markers of aging such as DNA damage or senescence, suggesting that it operates through a mechanism other than dietary restriction.”

“The implications of this study are significant, as they suggest that continuous chronic hypoxia could be a promising intervention to prolong lifespan and delay age-related neurological decline.. This finding may have implications for the development of targeted therapies for aging and age-related diseases in humans.. For example, living in conditions with restricted oxygen levels, such as at high altitudes or in mountainous areas, could extend life expectancy.. However, more epidemiological studies would be needed to verify this hypothesis,” he told SMC Spain.

“It is important to recognize that the precise mechanisms through which hypoxia exerts its effects are still unknown.. Further research is needed to fully understand these mechanisms and to evaluate the potential therapeutic applications of oxygen restriction in humans,” he added.

“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.. However, careful evaluation of the risks and benefits would be necessary to ensure the efficacy of such interventions in human populations.”