Molecular Mechanisms Linking Dietary Sugar to Metabolic Disorders, Inflammation, and Premature Aging

Abstract

Over consumption of dietary sugars, especially high fructose and sucrose, are now identified as one of the important factors contributing towards metabolic disturbance, chronic inflammation and accelerated aging process. Regular consumption of foods with high sugar content and sugar sweetened beverages is associated with obesity, insulin resistance, poor glucose tolerance, type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. The results of molecular research and studies on populations suggest that chronic high sugar feeding can cause metabolic dysfunction in several linked ways, such as poor insulin signaling, greater lipid production in the liver, more oxidative damage and less efficient mitochondria. Unlike glucose metabolism, fructose metabolism stimulates triglyceride deposition, uric acid formation and metabolic irregularities because it is largely metabolized in the liver without passing through critical steps in glycolysis. In addition, too much sugar activates inflammatory pathways such as NF-κB, MAPK pathways and the activation of the NLRP3 inflammasome, all of which play a role in chronic inflammatory reactions. Changes in gut microbes, combined with impaired gut barrier function may also amplify systemic inflammation and metabolic dysfunction. Moreover, chronic hyperglycemia is associated with increased generation of reactive oxygen species (ROS) and advanced glycation end products (AGEs) causing oxidative stress, DNA damage, dysfunction and senescence-related processes that increase the biological ageing process. High intake of sugar has also been shown to alter DNA methylation and histone modification, and it is emerging that these epigenetic changes may modulate the expression of genes related to metabolic and inflammatory pathways. Together, these findings indicate that chronic consumption of high-sugar diets has a wide-ranging molecular and physiological impact that negatively affects metabolic health and aging and suggest a need for nutritional intervention and prevention strategies to promote improved long-term health outcomes and healthy aging.