A Single gene Inactivation with implications to Diabetes and Multiple Organ Dysfunction Syndrome

Statement of the Problem: Specific genes that are involved in epigenetics are sensitive to nutritional regulation, oxidative stress and the development of insulin resistance that can result from changes in cellular chromatin structure, DNA methylation and histone modifications with relevance to the global chronic disease epidemic. Epigenetic modifications induced by unhealthy diets or environmental xenobiotics involve adipose tissue and liver with immune alterations that determine the survival of cells in various tissues. Methodology & Theoretical Orientation: Genomic analysis identify the defective gene in various chronic diseases as Sirtuin 1 (Sirt 1), a NAD(+)dependent class III histone deacetylase (HDAC) protein (1) that targets transcription factors to adapt gene expression to metabolic activity, insulin resistance and inflammation. Interests in Sirt 1 have increased since it may override the effects of other anti-aging genes (2) such as Klotho, p66Shc (longevity protein) and Fork head box proteins (FOXO1/FOXO3a). Findings: Unhealthy diets inactivate the calorie sensitive gene Sirtuin 1 (Sirt 1) involved in epigenetic processes that promote immune system alterations, mitochondrial apoptosis, non-alcoholic fatty liver disease, diabetes and nitric oxide (NO) modification with relevance to core body temperature (3) involved with appetite regulation, glucose homeostasis and hepatic xenobiotic metabolism (4). The interplay between NO and epigenetics has attracted interest with relevance to autoimmune disease and mitophagy (3) that has become of critical concern to diabetes and the development of multiple organ disease syndrome