Lipid requirements of autophagy in aging

Autophagy is a cellular process of nutrient recycling and stress defense and has recently brought into focus for prevention of aging and age-associated disease. It mediates the degradation of defective proteins and organelles, including protein aggregates and dysfunctional, potentially harmful mitochondria. Autophagy is controlled by the metabolic state of cells and its regulation depends on changes in amino acid and/or sugar metabolism. Much less is known about the role of lipids and their metabolism in autophagy regulation, although lipids are central molecules in the autophagy process, being part of autophagic membranes, signaling molecules and cargo. In this project in an (inter)national collaborative effort, we will use genetically tractable model systems (i.e. the budding yeast Saccharomyces cerevisiae and the fruit fly Drosophila melanogaster) to dissect the role of lipids and their metabolism in regulation of autophagy during aging. We aim to identify the specific types of lipids that are required for the induction of autophagy, formation and maturation of autophagosomes (the organelles that carry autophagic cargos) and their subsequent degradation within lysosomes/vacuole of the cell. We aim to characterize the metabolic pathways that are responsible for formation of these lipids and how precisely they intersect with the autophagic machinery. Efficient autophagic flux including the degradation of autophagosomes within lysosome/vacuole is required to allow the recycling of nutrients and successful cargo detoxification. Finally, using yeast and fly models of lipodystrophy, we will characterize the impact of lipid imbalance on autophagy and aging. Employing various lipid supplementation strategies, we aim to ameliorate lipid imbalances and restore or improve the autophagic competence of cells. The consequence of such treatments will then be tested for their impact on life and health span during aging.