Allostasis and Metabolic Resiliency in Older People

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DESCRIPTION (provided by applicant): Older people may be especially sensitive to environmental stressors due to diminished physical capabilities and an increased hypothalamo-pituitary-adrenal (HPA) axis sensitivity, resulting in repeated and prolonged hormonal responses to common day challenges. These repeated hormonal perturbations contribute strongly to what is now termed the allostatic load, which, in turn, precludes a cascade of primary events and secondary health consequences, such as dyslipidemia, excess visceral adiposity, and insulin resistance. Rarely is hyper-responsiveness to environmental stress and metabolic resiliency studied in older people and so, the purpose of this proposal is to determine the relation between stress response, fat metabolism, and insulin resistance in aging. Specific aims are: 1) to determine the association between subjective daily life experiences and the cortisol response curve to an acute psychophysical challenge in healthy and non-obese men and women 65 years of age and older; 2) to determine the effect of cortisol hyper-responsiveness on several functional indicators of lipolysis and insulin resistance in this same older sample; and 3) to determine the degree to which the relation between cortisol hyper-responsiveness and insulin resistance is modulated by growth hormone (GH) response to the psychophysical challenge and by levels of IL-6 and visceral adiposity in older age. We plan to use a recently-published hybrid method - the Day Reconstruction Method (DRM) - for gathering quantitative information about affective responses to daily life experiences that may be contributors to or consequences of a HPA hyper-responsiveness in aging and will use a novel psychophysical challenge with tasks that mimic common real life environmental situations, such as those encountered when driving an automobile. The automated psychophysical test (APT) is a computerized series of timed performance measures of simple reaction time, choice reaction, visual tracking, static and dynamic acuity, and information processing. In addition, we will use state-of-the-art methods for the quantification of visceral adiposity (CT scan) and the indicators of lipolysis and insulin resistance (the hyperinsulinemic-euglycemic clamp with tracer infusions for determination of hepatic glucose production and peripheral lipolysis) in order to determine the health and functional consequences associated with a negative response to common daily challenges.