The role of Klotho and sirtuins in sleep-related cardiovascular diseases: a review study

The prevalence of sleep disorders has been reported from 1.6% to 56.0%, worldwide. Sleep deprivation causes cardiovascular diseases (CVDs) including atherosclerosis, vascular aging, hypertension, heart dysfunction, reduced heart rate variability, and cardiac arrhythmia. Reduced tissue oxygen causes various CVDs by activating pro-inflammatory factors and increasing oxidative stress. Sleep disorders are more important and prevalent in older people and cause more severe cardiovascular complications. On the other hand, the reduction of Klotho level, an age-dependent protein whose expression decreases with age, is associated with age-related diseases. Sirtuins, class III histone deacetylases, also are among the essential factors in postponing cellular aging and increasing the lifespan of organisms, and they do this by regulating different pathways in the cell. Sirtuins and Klotho play an important role in the pathophysiology of CVDS and both have anti-oxidative stress and anti-inflammatory activity. Studies have shown that the levels of Klotho and sirtuins are altered in sleep disorders. In this article, alterations of Klotho and sirtuins in sleep disorders and in the development of sleep-related CVDs were reviewed and the possible signaling pathways were discussed. The inclusion criteria were studies with keywords of different types of sleep disorders and CVDs, klotho, SIRT1-7, and sirtuins in PubMed, Scopus, Embase، Science Direct، Web of Sciences and Google Scholar by the end of 2023. The studies revealed there is a bidirectional relationship between sleep disorders and the serum and tissue levels of Klotho and sirtuins and sleep related-CVDs.