The Role of Epigenetic Regulator SIRT1 in Balancing the Homeostasis and Preventing the Formation of Specific "Soil" of Metabolic Disorders and Related Cancers

Abstract

SIRT1 was discovered in 1979 but growing interest in this protein occurred only 20 years later when its overexpression was reported to prolong the lifespan of yeast. Since then, several studies have shown the benefits of its increased expression in preventing or delaying of many diseases. SIRT1, as a histone deacetylase, is an epigenetic regulator but it has wide range of non-histone targets which are involved in metabolism, energy sensing pathways, circadian machinery and in inflammatory regulation. Disturbances in these interconnected processes cause different diseases, however it seems they have common roots in unbalanced inflammatory processes and lower level or inactivation of SIRT1. SIRT1 inactivation was implicated in coronavirus disease (COVID-19) severity as well and its low level counted as a predictor of uncontrolled COVID-19. Several other diseases such as metabolic disease, obesity, diabetes, Alzheimer's disease, cardiovascular disease or depression are related to chronic inflammation and similarly show decreased SIRT1 level. It has recently been known that SIRT1 is inducible by calorie restriction/proper diet, physical activity and appropriate emotional state. Indeed, a healthier metabolic state belongs to higher level of SIRT1 expression. These suggest that appropriate lifestyle as non-pharmacological treatment may be a beneficial tool in the prevention of inflammation or metabolic disturbance-related diseases as well as could be a part of the complementary therapy in medical practice to reach better therapeutic response and quality of life. We aimed in this review to link the beneficial effect of SIRT1 with those diseases, where its level decreased. Moreover, we aimed to collect evidences of interventions or treatments, which increase SIRT1 expression and thus, open the possibility to use them as preventive or complementary therapies in medical practice.

Keywords: SIRT1; cancer prevention; health; lifestyle; metabolism; methylation.