Can Less Oxygen Extend Lifespan? Scientists Find Surprising Result in Progeroid Mice

Scientists have discovered that extended lifespan and neurological function in mice can be attained through continuous oxygen restriction, according to a study published in the journal PLOS Biology. However, while it is known that hypoxia reduces oxygen levels in the body, the mechanism behind the effects on longevity remains uncertain. The study found that mice in a setting where oxygen concentration was cut is half excited the median lifespan of the progeroid mice by 50%, a “compression of mortality” effect, which is more impactful on healthspan than on maximum lifespan. Although hypoxia increased the body weight of the rodents, their mice were stronger. Furthermore, they also did not exhibit a reduction in calorie intake, as would ordinarily be the case with anti-aging dietary practices such as caloric restriction.

Health benefits of mild hypoxia
Hypoxia, meaning low blood oxygen levels, is not beneficial in most cases, with acute hypoxia capable of causing significant organ damage and even death. However, research has highlighted long-term early mild hypoxia as being beneficial, depending on specific contexts. Epidemiological data suggests that living in a high-altitude environment helps to improve healthspan and potentially lifespan, while some athletes train in such environments to improve cardiovascular fitness.
Burrowing mammals are among the long-lived species, including the naked mole rat, which lives in highly hypoxic environments. However, the effects of chronic, continuous hypoxia on mammalian lifespan have not been extensively investigated. Research has found that mammalian cells grown under chronically continuous hypoxia conditions enter replicative senescence later, while the same conditions have also been found to extend the lives of simpler animal models such as fruit flies, nematode worms, and yeast.

The study
In this study, genetic modification was used on progeroid mice (Ercc1 Δ/- mice), which experience early aging but do not have any physical disabilities on birth. The study set those mice in a chamber with a reduced oxygen concentration of 11% from the 21% normally breathed, before the first sign of premature aging emerged, which usually occurs around four weeks of age. Although the increase in maximum lifespan was less dramatic, there was a noticeable effect on compression of mortality, with progeroid mice living 50% longer under continuous hypoxia. However, researchers did not detect any significant or considerable differences in DNA damage markers or classic senescence markers between both groups. Further research is needed to investigate a combination of hypoxia and caloric restriction and biomarkers such as DNA damage and to compare aging in normally aging mice to progeroid mice.

Implications of the study
This study highlights the potential of mild hypoxia for increasing longevity in humans and could lead to further research into the effects of continuous hypoxia on human longevity. While it is worth noting that progeroid mice are not a good model for fully replicating natural aging, the data suggests that mild hypoxia could have significant impacts on mitigating aging-related challenges. There is a possibility that the study could lead to human trials in the future, particularly regarding how those living at high altitudes respond to low oxygen environments.