Fig. 6

Proposed model of epigenetics-regulated autophagy impairment in obstructive sleep apnea (OSA) and its clinical phenotypes. A schematic diaphragm depicts probably contributing effects of hypermethylated LC3B gene promoters and hypomethylated p62 gene promoters on the development of OSA and EDS/nocturia/depression/cognitive dysfunction phenotypes through inhibiting autophagy. In contrast, chronic intermittent hypoxia in OSA patients may lead to hypermethylated ATG5 gene promoters, which probably contribute to the development of morning headache, memory impairment, and fatigue through down regulating ATG5. Autophagy enhancer (rapamycin), mesenchymal stem cell, and re-methylation agent (folic acid) treatment may reduce late apoptosis and oxidative stress through augmenting autophagy. Red arrows indicate predisposition, and orange arrows indicate cause and effect relationships