Calorie Restriction, Body Temperature and Alzheimers Disease

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Calorie restriction (CR) has anti-aging effects, prolongs lifespan and reduces the incidence of age associated diseases. Experimental evidence in animal models indicates that CR ameliorates the neuropathologic and behavioral abnormalities seen in transgenic models of Alzheimer’s disease (AD). Our previous work demonstrated that one mechanism by which CR promotes longevity is by reducing core body-temperature (Tb). Since virtually all proteins are sensitive to heat denaturation, nature has created cellular systems to protect cells from even small quantities of abnormally folded toxic proteins as far back in evolution as bacteria. We now hypothesize that the beneficial effects that CR has on the AD models are at least in part due to its ability to reduce Tb and the subsequent proteotoxic stress. Here we propose experiments to test our hypothesis regarding the role of lowering body temperature as being a major factor in both life extension and the salutary effect of CR in the well validated Tg2576 transgenic model of human AD.