The purpose of the Healthspan and Functional Assessment Core is to provide researchers in aging with measures of the functional status of animal models of aging by assessing the performance of an array of organs and physiological systems. Emphasis is on functions known to be altered with age or in age-related diseases and that may be important in the health of mice and/or humans.
The Specific Aims of the Healthspan and Functional Assessment Core are to provide the following: 1. Assessment of endocrine/ metabolic function and body composition/structure. In humans, resting metabolic rate (MR), activity, and rhythmicity of activity patterns decline with age. We will assess these parameters by using our metabolic cage system (Sable Systems). As changes in endocrine/metabolic function are closely tied to changes in body composition, we will also provide investigators with tools to measure whole body and regional lean and fat mass and measures of bone mineral density. We will also provide support for performing tests of glucose utilization and insulin sensitivity, including the hyperinsulinemic euglycemic clamp for testing insulin sensitivity of different tissues. 2. Measures of cardiovascular function. It has become clear in recent years that while mice do not develop hypertension they are prone to some of the same cardiac changes with age as are humans, including age-related cardiac muscle atrophy, increased fibrosis, and a decrease in diastolic function and ejection fraction. Thus, we will provide investigators with the tools and expertise to measure a variety of cardiac parameters using our state-of-the-art Vevo 770? High-Resolution in vivo Imaging System (Visual Sonics). Moreover, a pharmacological version of a cardiac stress test can be made on lightly anaesthetized mice treated with dobutamine, which temporarily increases heart rate and thus acts as a stressor. 3. Tests of locomotor behavior and cognitive health. Balance, coordination, flexibility, strength, and endurance all decline with age. Therefore the Core will provide assays of neurological, neuromuscular, skeletal muscle, and joint health. Different dimensions of cognitive health will be assessed by passive avoidance, contextual fear conditioning, and the Barnes maze and Morris water maze. 4. Education and consultation to core users. A major function of the core, will be to provide the appropriate expertise and education on the use of these tools both to help investigators gather preliminary data for grant applications and to help investigators with manuscript preparation.
In the US, the increasing age of the population is a major risk factor for morbidity and most common diseases such as atherosclerosis, cancers, Parkinson's disease, dementia, and metabolic syndrome. Treatments that increase that portion of the lifespan free of disabling morbidity, i.e., healthspan, in mice, will suggest research directions leading to clinical treatments designed to prevent or retard deleterious changes with age.
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