Chronic intermittent hypoxia leads to disruption of clock genes expression in mouse lung tissues: Potential consequences on lung cell senescence

Obstructive sleep apnoea (OSA) syndrome is a common sleep disorder in which recurrent apnoea and hypopnoea produce repeated episodes of hypoxemia followed by reoxygenation. We previously demonstrated that OSA was associated with telomere shortening and increased susceptibility to cell senescence [1]. The cyclin-dependent kinase inhibitor p21, the main effector of p53, is activated in response to DNA damage and telomere dysfunction but is down-regulated by certain clock genes. Sleep abnormalities also disrupt endogenous circadian clock genes, more specifically Rev-Erbα, a central transcriptional repressor of the molecular clock that downregulates p21 expression.