Oxidative mtDNA damage is a recognized pathogenetic mechanism of aging in mammals. Progressive degradation of mitochondria underlies oxidative stress, which causes accumulative molecular damage, genomic instability, telomeres shortening, metabolic and hormonal decline, accelerates protein glycation and diminishes protein turnover. Continuous rejuvenation of mitochondria in somatic cells can reduce oxidative stress, increase efficiency of oxidative metabolism, slow down aging process, prevent and/or retard development of age-related pathology.
A natural mechanism (mitoptosis) recently discovered in mammals facilitates continuous purification of the mitochondrial pool in an organism from the most ROS-producing mitochondria. Mitoptosis selectively eliminates them, thus providing advantage for proliferation of wild-type (non-mutated) mtDNA. Mitoptosis can be induced by time - and pO2 tension-controlled cycling of intracellular pO2 from normoxic to hypoxic state and back in the range between 5 - 1 torr. Such O2 oscillations can be safely induced by Intermittent Hypoxic Therapy/Training (IHT).
IHT is a novel preventative, therapeutic and rehabilitative treatment that has been developed and refined during the last decades. IHT improves autonomic homeostasis, modulates humoral and cellular immunity and markedly augments non-specific stress-resistance. This brings measurable rejuvenative effects and rapid clinical improvements in numerous diseases, physical and mental conditions. The ability to regulate, adjust and balance metabolism via hypoxic preconditioning that modifies the cellular and mitochondrial life cycle through nitric oxide pathway is the most valuable property of IHT. The cellular and systemic effects of hypoxic preconditioning include: a) rejuvenation of mitochondria via mitoptosis; b) decrease of reactive oxygen species generation; c) increased enzymatic antioxidative defense; d) decreased lipid peroxidation; e) improved oxygen absorption, transportation and utilization; f) improved glucose metabolism and enhanced accumulation of intracellular glycoge! n; g) increased accumulation of cytoglobins; h) increased erythropoetin and Hsp -70 levels; i) facilitated mesenchimal stem cells-dependent tissue repair.
Technically, the IHT session consists of 6 - 10 controlled repeated hypoxia-reoxygenation episodes: 2 - 6 min. intervals of hypoxic air inhalation, interspersed with 3 - 5 min. intervals of normoxic or hyperoxic air inhalation. Several times a week training for 2 - 4 weeks gradually induces beneficial clinical effects. The effects of IHT in healthy subjects are moderately expressed, while they are clearly noticeable in patients, suffering from oxidative stress. To achieve better results from IHT the individualized protocols should be used. The efficiency of IHT can be enhanced by intermittent caloric restriction and by synergistic nutraceutical supplementation.
Results of the treatment of 102 patients are discussed. A detailed description and analysis of several clinical cases is provided.
Prokopov A. Exploring overlooked natural mitochondria - rejuvenative intervention. The puzzle of bowhead whales and naked mole rats. Rejuvenation Res 2007, in press.
