Project 459577

Hyperglycemia (high glucose concentration) is associated with metabolic and age-related disorders. Chronic hyperglycemia is responsible for insulin resistance, obesity, hypertension, and neuropathies, leading to tissue damage and fatal outcomes. However, glucose is not a toxic molecule per se. Its metabolic function is critical to fuel cellular processes involved in cell defenses and is crucial for the appropriate development of any living organism. Indeed, the metabolic efficacy of a cell profoundly influences how long and how well it endures the different stress encountered during its lifetime. Our initial work has shown that a short high-glucose diet during development can increase health and life in the nematode Caenorhabditis elegans. This 1 mm long worm is a uniquely powerful model organism to investigate metabolic processes in the context of aging. Its short life (about 21 days) and simple genetic have helped answer numerous questions in the context of aging. The proposed research focuses specifically on determining how glucose can enhance cellular resistance to metabolic and age-associated dysfunctions and the mechanisms underlying such protective responses. I will use an integrative approach relying on profiling both the transcriptome and metabolome of glucose-treated worms to provide a comprehensive picture of the mechanisms responsible for the glucose-mediated health response. Furthermore, we also attempt to describe when these protective mechanisms are lost and the potential targets with a therapeutic potential to reduce the incidence of metabolic and age-related disorders. The expected outcomes are a better understanding of the cellular, and the metabolic, components with therapeutic potential in the context of aging-related disorders such as Alzheimer's and Parkinson's Disease or Type II diabetes.