PPARγ and stress: implications for aging

Abstract

Complex interactions link psychological stress and aging - stress generally promotes aging processes, and conversely, aging can contribute to stress dysregulation. Stress and aging have remarkably similar effects on brain. Both induce neuroinflammation and alter neuronal metabolism and activity, which to varying extents are causally-linked to the development of stress and aging pathology. As such, induction of one or more of these brain disturbances by either stress or aging could predispose for the development of dysfunction in the other. Notably, peroxisome proliferator-activated receptor γ (PPARγ) is expressed in brain regions that regulate both stress and aging (e.g., hippocampus) and can act to prevent the consequences of aging and stress on the brain. In addition, PPARγ agonists reduce the physiological stress response itself. Thus, PPARγ may represent a critical mechanistic link between brain aging and stress that could hold therapeutic potential for the prevention and treatment of age-related cognitive and mood disorders.