Researchers here show that a mouse model of accelerated aging lives considerably longer when in a low-oxygen atmosphere for most of its life span. This is quite interesting, even given that large effect sizes in accelerated aging models should be taken with a grain of salt. It is most likely that any effect on normal mice would be smaller, and also likely that any form of life extension achieved through manipulation of stress responses, such as the response to hypoxia, will produce much smaller effects in long-lived mammals than in short-lived mammals.
As is always the case, recall that when we say "accelerated aging" what we really mean is that the mouse lineage in question exhibits some deficiency that allows one specific form of cellular dysfunction to accumulate rapidly. These models can appear a little like accelerated aging, but they are not actually exhibiting accelerated aging, just the accumulation of one form of damage. Normal aging is a mix of numerous different types of cellular dysfunction and damage, and that difference matters. In this case, the model has a mutation that impairs DNA repair. The large effect size for hypoxia in this model in turn might imply that hypoxic stress is good at improving DNA repair efficiency, but more research would be needed to confirm that hypothesis.
Hypoxia extends lifespan and neurological function in a mouse model of aging
To the best of our knowledge, the current study is the first to report that hypoxia extends lifespan in a mouse model of aging. We have demonstrated that continuous hypoxia (11% oxygen) - or "oxygen restriction" - significantly extends lifespan of Ercc1 Δ/- mice and delays neurologic morbidity. In this model, hypoxia appears to be the second strongest intervention to date, second only to dietary restriction.
Our findings add to a nascent but burgeoning literature on the beneficial effect of hypoxia in a wide variety of neurologic disease models. Chronic continuous hypoxia has been reported as beneficial in at least three other mouse models of neurologic disease. In two mitochondrial disease models, hypoxia corrects defects that arise as a consequence of the genetic lesion. In the experimental autoimmune encephalitis model of multiple sclerosis, continuous 10% oxygen promotes vascular integrity and apoptosis of infiltrating leukocytes. The ability of hypoxia to alleviate brain degeneration in such diverse models points either to the pleiotropic effects of oxygen restriction, or alternatively, the existence of a downstream and convergent neuroprotective mechanism.
An important future goal is to define the mechanism by which chronic continuous hypoxia is extending lifespan in this model, and the extent to which this mechanism overlaps with that of pathways known to be involved in aging, such as mTOR and insulin signaling. Three plausible mechanisms are the following: (i) activation of the HIF pathway; (ii) diminution of oxidative stress; and (iii) interruption of the vicious cycle of neurodegeneration and neuroinflammation.
Epidemiologic evidence suggests that lifelong oxygen restriction might slow the aging process in humans. Though there are many potential confounders to this finding, recent cross-sectional studies in Bolivia have demonstrated significant enrichment for nonagenarians and centenarians at very high altitudes. There is also intriguing data that suggests there are potential benefits of moving to altitude in adulthood. In a longitudinal study of over 20,000 soldiers of the Indian Army assigned to serve at 2 to 3 mile elevations above sea level for 3 years between 1965 and 1972, their risk of developing the major sources of age-related morbidity in modern societies was a fraction of the risk of their comrades serving at sea level.
View the full article at FightAging
