Alterations of Sleep and Circadian Timing in Aging

The application focuses on the interactions between peripheral tissue clocks, sleep and centrally regulated circadian rhythms in the age-related increase in metabolic disease. A multi-disciplinary and multi-institutional (Northwestern and U of Chicago) approach combining basic (Project 3), translational and clinical (Projects 1 & 2) studies will employ genetic, biochemical, molecular and integrative physiologic approaches to determine the role of age-related clock system disruption on the deterioration of cardiometabolic health, sleep and circadian rhythms in aging. In addition, Projects 1 and 2 will test the hypothesis that interventions aimed to enhance clock function will decrease the risk or severity of metabolic disease in older adults. Our program is unified by the following shared research objectives: • To define the role of interplay between central and peripheral clocks in aging. • To define the role of metabolic status on regulation of sleep/wake and of sleep/wake status in regulating metabolism. • To understand the relative significance of age-related changes in the clock system: amplitude, phase alignment, sensitivity. To achieve these goals, we propose the following components and leadership: Program Director: Phyllis C. Zee (Northwestern University) Core A (Administrative Core): Phyllis C. Zee (Northwestern University) and Eve Van Cauter (U of Chicago) Core B (Methods and Analysis Core): Eve Van Cauter (U of Chicago) Core C (Metabolic and Molecular Laboratory Core): Joseph Bass and Ravi Allada (Northwestern University) Project 1: (Enhancing Circadian Signal to Improve Cardiometabolic Function in Aging): Phyllis C. Zee (Northwestern University) Project 2: (Behavioral Chronotype: Impact on Sleep and Metabolism): Eve Van Cauter and Kristen Knutson (U of Chicago) Project 3 (Crosstalk between Peripheral and Neuronal Clocks in Sleep and Metabolic Aging): Joseph Bass and Fred Turek (Northwestern University)