Intermittent hypoxia and health: From evolutionary aspects to mitochondria rejuvenation

Abstract

Mitochondrial aging manifests as gradual depletion of energy reserves at cellular and -systemic levels, as well as lowered stress resistance. Vital functional state of mitochondria is essential to reduce burden of age-dependent degenerative diseases and prolong health span. Two mitochondria-rejuvenating interventions: intermittent hypoxic training (IHT) and extended morning fasting (EMF), as engineered derivates of naturally occurred intermittent oxygen restriction (IOR) and intermittent calorie restriction (ICR), have been already in clinical practice. IHT and EMF utilize the familiar developmental and adaptational genetic programs, evolutionarily preinstalled in all aerobic organisms. Both ICR and IOR employ a common mitochondria-rejuvenating pathway, the mitoptosis - a selective elimination of the mitochondria that excessively produce reactive oxygen species in the cells. Mitoptosis is a natural process that maintains quality of mitochondria in the female germinal cells during early embryogenesis and can be stimulated and maintained by IOR and ICR also in postmitotic cells of adult organisms. ICR and IOR synergistically diminish the basal level of mitochondria-dependent oxidative stress that is supposed to be the key factor modulating life span and health span in aerobes. Furthermore, ICR and IOR influence longevity and tempo of development of age-related diseases via several mitochondria - independent pathways, such as suppressed protein glycation, enhanced DNA repair, accelerated protein turnover, stimulation of erythropoetin, growth hormone, heat shock protein 70, and other functional proteins. In addition, the IOR specifically intensifies stem cells-dependent tissue repair. The synergistic application of IOR- and ICR-based protocols, accompanied by nutrigenomical adjustment and individualized nutraceutical supplementation, brings multiple health benefits and alleviation or cure in numerous chronic degenerative and age-related diseases. Further development of engineered ICR and IOR protocols should help their advanced clinical implementation and user-friendly, self-help applications.