The potential role of mitochondria in age-related health benefits conferred by moderate hypoxia.

Background Mitochondrial integrity and efficiency deteriorate with age and are linked to cellular senescence. Mitochondria are highly responsive to reduced oxygen availability (hypoxia), which for example occurs when exposed to altitude. We hypothesize that mitochondria are involved in the observed health benefits at moderate altitude. Because the experimental evidence on mitochondrial changes at moderate altitude is limited, we also evaluate dose-response associations of oxygen transport and mitochondrial functions derived from measurements at normoxia and severe hypoxia. Summary We summarize the effects of environmental oxygen availability and changes in cellular oxygen demand/supply on mitochondrial functions and assess, how this may influence aging. Hypotheses are presented how mild hypoxia at moderate altitude (1000 - 2500 m) could improve mitochondrial function and possibly explain the reported lower levels of mortality from several age-related diseases. Key messages It is unknown, whether continuous or intermittent types of hypoxia exposure are more effective in improving mitochondrial functions and promoting healthy aging. The combination of tissue-specific oxygen demand (for example during physical exercise) with mild reductions of ambient oxygen availability may enable the reported health benefits associated with moderate altitude residence.