June 22, 2024

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Harvard: Hypoxia Extends Lifespan and Improves Brain Function

Harvard: Hypoxia Extends Lifespan and Improves Brain Function


Harvard: Hypoxia Extends Lifespan and Improves Brain Function


For the vast majority of life on Earth, oxygen is undoubtedly an essential factor for survival.

Without water and food, you can survive for several days, but without oxygen, a few minutes is enough to suffocate you to death.

This is because the metabolism of cells must have enough oxygen, and various nutrients must be combined with oxygen to release energy. .


However, on the early Earth, all organisms were anaerobic, and oxygen was highly toxic to early life (anaerobic bacteria) .

It’s just that during the long evolution process, life on earth gradually fell in love with this “poison”, and it got out of control. Up to now, most of the creatures on the earth have become “aerobic creatures”.


At this point, is oxygen really no longer harmful? Even after a long evolution, does oxygen just change from a deadly poison to a chronic poison, ending a person’s life in an average of 80 years?


On May 23, 2023, researchers from Massachusetts General Hospital of Harvard Medical School published in the journal PLOS Biology entitled: Hypoxia extends lifespan and neurological function in a mouse model of aging (In the aging mouse model, hypoxia prolongs Research Paper on Lifespan and Neurological Function) .


The study shows that oxygen really seems to be a “chronic poison”: in a mouse model of aging (Ercc1Δ/- mice) , chronic persistent hypoxia (11% oxygen concentration, equivalent to the oxygen concentration at Everest Base Camp) It can extend the lifespan of mice by 50% and improve the neurological function of old mice.

This is the first time “oxygen limitation” has been shown to be beneficial in a mammalian model of aging.


Harvard: Hypoxia Extends Lifespan and Improves Brain Function

With the intensification of the global aging wave, anti-aging research has become one of the most popular research fields. Numerous research efforts have identified compounds that extend healthspan and show exciting effects in mammalian experimental models.

For example, metformin is currently undergoing human clinical trials in older adults to assess its potential impact on morbidity and mortality from common age-related chronic diseases.


It is worth noting that among a series of antiaging interventions, Dietary Restriction (DR) stands out.

Both have life-prolonging effect. This makes people think deeply, dietary restriction is reflected in the control of the body’s metabolism, so can oxygen restriction also have the same effect?


Indeed, previous studies have shown that oxygen limitation is associated with increased lifespan in yeast, nematodes, and fruit flies, but its effects in mammals have so far remained unknown.

To explore the anti-aging potential of oxygen limitation in mammals, the research team selected aging mouse models as research subjects. typical features.


Harvard: Hypoxia Extends Lifespan and Improves Brain Function

Oxygen limitation (11% oxygen concentration) significantly extends lifespan in mice


The researchers fed these aging-prone mice under different oxygen concentrations.

Aging mouse models living at 11% oxygen concentrations (similar to the oxygen concentration at Everest Base Camp at an altitude of 5,200 meters) lived longer than mice living at normal oxygen concentrations (21% ) , with an average lifespan of 23.5 weeks, while the lifespan of these mice was only 15.7 weeks under normal oxygen levels, which is equivalent to extending their lifespan by 50% by restricting oxygen.


Harvard: Hypoxia Extends Lifespan and Improves Brain Function

Oxygen limitation improves neurological function in a mouse model of aging


Given that previous studies have shown that dietary restriction can also extend the lifespan of aging mice, the research team wondered whether oxygen restriction could extend the lifespan of the animals simply by changing their eating habits.

However, they found that oxygen restriction did not affect the mice’s food intake, nor did it significantly affect markers of DNA damage or aging.


This suggests that oxygen limitation does not merely mitigate the direct effects of Ercc1 mutations, but acts downstream through unknown mechanisms, resulting in increased lifespan in Ercc1Δ/- mice.


Harvard: Hypoxia Extends Lifespan and Improves Brain Function

Effects of oxygen limitation on the cerebellar transcriptome


Chronic persistent hypoxia has been reported to be beneficial in at least three other mouse models of neurological disease, said Robert Rogers, Ph.D., lead author of the paper.

In these different models, the ability of hypoxia to attenuate brain degeneration either suggests the effects of oxygen limitation.

Pleiotropic effects, either suggest the presence of downstream and convergent neuroprotective mechanisms.


Interestingly, the life-extending effect of oxygen limitation has also been shown in humans.

For example, a recent study in Bolivia showed a significant increase in the number of 90-year-olds and centenarians at high altitudes.

Moreover, moving to high altitudes as adults may have health benefits: A longitudinal study of more than 20,000 Indian Army soldiers between 1965 and 1972 found that soldiers stationed at high altitudes suffered from diabetes, hypertension and ischemia lower risk of diseases such as heart disease.


Cumulative distribution function of gene expression in the cerebellum as a function of gene length


Taken together, these findings support the anti-aging potential of oxygen limitation in mammals and even humans.

Of course, further studies are needed to elucidate the life extension effect of oxygen limitation, for example, what is the specific molecular mechanism, how much does this mechanism overlap with the known signaling pathways related to aging, and whether this mechanism is in Works effectively in all organs.


Dr. Robert Rogers , Long-term living at 11% oxygen is too difficult for most people, to determine if more practical hypoxic regimens such as intermittent hypoxia or moderately low oxygen levels (17% oxygen) are equally possible Prolonging life is very important.







Paper link :


Harvard: Hypoxia Extends Lifespan and Improves Brain Function

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