Interplay of chaperone-mediated autophagy with lipid metabolism and ER stress

Metabolic diseases, mainly associated to life-style (high fat, cholesterol, sugary diets, smoke or lack of physical exercise), is the main cause of death in the western and developing countries. For example, high glucose in diabetic patients contributes to deterioration of the blood vessels resulting in atherosclerosis and high cholesterol levels lead to vessel occlusion that can trigger further devastating consequences such as heart attack or stroke. Our body counts on systems that assure maintenance of proper metabolism but they malfunction with age explains the increased incidence of metabolic diseases in elders. This work intends to understand how autophagy, one of the basic systems that control metabolism in the cell, normally protects different organs against nutritional transgressions and how the gradual decrease in its function with age makes old organisms vulnerable to these nutritional insults and disease. Autophagy regulates metabolism by facilitating the break-down and recycling of parts of the cells (proteins, fat and sugars) to produce energy. We have previously found that autophagy decreases with age in some organs and we propose now that autophagy is key to make organs resistant to metabolic disease such as atherosclerosis or diabetes. We intend to identify in which organs the decrease of autophagy with age is more critical and may contribute to the development of these diseases. We expect that our study could set the basis for future methods to restore autophagy in old individuals that could be used in the treatments of diabetes and other metabolic disorders common in our elders.