FIGURE 1.

Hypoxia-Based interventions and ageing. Training in hypoxia has been shown as a safe therapy assessed through cardiac and pulmonary outcomes. Besides, substantially greater hypoxemia appears in elderly female compared with male, being need longer expositions in elderly male. Health benefits following exposure to hypoxia-based interventions in older people have been repeatedly reported (cardiometabolic effects, physical or cognitive performance are some examples). Different hypoxic exposure approach could have a different influence about hypoxia inducible factor (HIF): under normoxia (21% of fraction of inspired oxygen (FiO₂)), proline hydroxylase (PHD) mediates the binding of the E3 ubiquitin ligase pVHL with HIF-a for proteasomal degradation in the presence of oxygen and iron; under hypoxic conditions (9%–16% FiO₂), the hydroxylation of HIF-a is inhibited and it accumulates in the cytoplasm. Then, it translocates to the nucleus, where it dimerizes with the HIF-b subunit, binding to a highly conserved hypoxia response element (HRE) within promoters of hypoxia-responsive gene; under hyperoxia conditions (30%–40% FiO₂), there is an exponential increase in reactive oxygen species (ROS), which inhibit PHD, allowing HIF to accumulate and translocate to the cell nucleus. Created with BioRender.