Over the last century, many studies have demonstrated that calorie restriction (i.e. decreased food intake) and exercise cause lifespan extension in model organisms and decrease human mortality from age-associated diseases. Many physiological changes in response to calorie restriction and exercise have been identified, however, it is still unknown which specific changes in metabolism drive these beneficial effects on aging. To address this question, I am using two parallel approaches. First, I am developing a suite of novel genetically encoded tools for manipulation of key metabolic parameters (e.g. NADH/NAD+ ratio) in live cells that will allow us to establish the causal relationships between specific changes in metabolism that are observed with calorie restriction or exercise and their effects on lifespan and other age-associated phenotypes. Second, I am building novel kinetic models of energy metabolism that will allow us to characterize the regulation of energy metabolism pathways by making quantitative predictions of reaction rates and metabolite concentrations in live cells. Together, these studies aim to uncover novel mechanisms of regulation of energy metabolism and their role in the aging process.
Speaker: Denis Tetov, UC Berkeley
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