Oxygen restriction for a longer and healthier life
Nothing is as important to us as oxygen, yet we only have a supply that lasts for a few minutes. This gas that we are so extremely dependent upon, why don't we store more of it in our bodies? In the same way that we store large amounts of fat, glucose, proteins, water, and other life-sustaining substances. The very thing we need the most we have the least of. What is the logic behind this? One reason is obviously because it is so easily available as there is 21% oxygen in the air we inhale.
Another important reason is that oxygen is very reactive and that too much oxygen is toxic and dangerous. If we bite an apple and put it down, the pulp will turn brown after just a few minutes. This is because it is exposed to oxygen. When we wrap our food in plastics it protects the food from oxygen and prevents it from decaying. The biological process that happens in the apple when it turns brown is the same process that happens inside our body.
Oxygen is indeed a double-edged sword. On the one hand, we thrive on oxygen as we need it to produce energy efficiently. If the supply is cut off, we die within minutes. On the other hand, oxygen is very reactive, and too much oxygen is toxic and dangerous.
One of the great scientific discoveries is that oxidative stress is linked to almost every disease and symptom known to man. As oxygen is a very reactive gas, excess leads to an increased amount of free oxygen radicals, also known as oxidative stress. When free radicals, oxidation, form in the body, inflammation increases. If oxidation is taking place at a higher rate than the body can handle, the aging process is accelerated.
Low-oxygen environment increased lifespan by 50%
A recent study explored how oxygen restriction (chronic hypoxia) affects lifespan and neurological function in mice.
“Epidemiological studies have hinted that populations that live at higher altitudes tend to live longer and stay healthier as they age. We wanted to test whether, in a more controlled setting, restricting oxygen appears to do the same in our mouse model of aging”, said study senior author Vamsi Mootha, professor of systems biology at the Blavatnik Institute at Harvard Medical School.
Key takeaways:
The researchers utilized a strain of mice known for its accelerated aging, to test whether continuous exposure to low oxygen (11%) could delay aging-related decline. The study found that mice subjected to hypoxia lived 50% longer and demonstrated delayed neurological deterioration, particularly in motor coordination.
Oxygen restriction more important than calory restriction
Interestingly, the researchers found that these mice maintained normal food intake, ruling out caloric restriction as the primary cause for their increased longevity. This finding points to the involvement of other biological pathways triggered by reduced oxygen availability, which might influence metabolic and cellular processes. Oxygen deprivation, in this context, could stimulate protective mechanisms that enhance cellular health and delay age-related deterioration.
The study's findings suggest that oxygen restriction could be a potent anti-aging strategy, analogous to dietary restriction, but with distinct mechanisms. While other studies on anti-aging have often targeted nutrient sensing and metabolic pathways like mTOR, this research focuses on oxygen homeostasis, an area relatively unexplored in mammals. The results highlight hypoxia's potential in reducing oxidative stress and managing neuroinflammation—factors closely tied to aging.
Hypoxia enhances brain function
In addition to lifespan extension, low-oxygen conditions enhanced motor performance and neurological resilience in aging mice. This improvement in brain function under hypoxia is notable since brain degeneration is a prominent feature of aging in both humans and mice. Despite the observed benefits, the research did not find significant changes in DNA damage markers or in gene expression linked to oxidative stress, implying that other pathways might be at play.
Another significant finding was that continuous hypoxia led to increased hematocrit levels, a common response to low oxygen. However, in these mice, the increase was unusually pronounced, possibly contributing to enhanced oxygen delivery to tissues. The study suggests that maintaining reduced oxygen levels may help break the cycle of neuroinflammation and degeneration, offering a novel therapeutic avenue for combating age-related decline.
Scientific references
Title: Hypoxia extends lifespan and neurological function in a mouse model of aging
Author: Robert Rogers et al
Link to fulltext: PLOS Biology May 2023
Abstract: There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence in cultured cells and extends lifespan in yeast, nematodes, and fruit flies.
Here, we asked whether chronic continuous hypoxia is beneficial in mammalian aging. We utilized the Ercc1 Δ/- mouse model of accelerated aging given that these mice are born developmentally normal but exhibit anatomic, physiological, and biochemical features of aging across multiple organs.
Importantly, they exhibit a shortened lifespan that is extended by dietary restriction, the most potent aging intervention across many organisms. We report that chronic continuous 11% oxygen commenced at 4 weeks of age extends lifespan by 50% and delays the onset of neurological debility in Ercc1 Δ/- mice.
Chronic continuous hypoxia did not impact food intake and did not significantly affect markers of DNA damage or senescence, suggesting that hypoxia did not simply alleviate the proximal effects of the Ercc1 mutation, but rather acted downstream via unknown mechanisms.
To the best of our knowledge, this is the first study to demonstrate that “oxygen restriction” can extend lifespan in a mammalian model of aging.
