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Activation Of SIRT1 Through Calorie Restriction Or Drug Treatment Delays Neurodegeneration In Experimental
Activation of SIRT1 through calorie restriction or drug treatment delays neurodegeneration in experimental model
Tuesday, May 21, 2013. The May 22, 2013 issue of the Journal of Neuroscience includes an article by researchers at the Massachusetts Institute of Technology (MIT) which reports an association between a calorie restricted diet and a delay in the decline in brain function that occurs in a mouse model of neurodegeneration. The study utilized a breed of mice in which neurodegeneration is induced by administration of the drug doxycycline. Li-Huei Tsai, PhD of the Picower Institute for Learning and Memory, Howard Hughes Medical Institute, and Broad Institute of Harvard University and Massachusetts Institute of Technology and associates fed the animals a diet which reduced by 30 percent the amount of calories that would have been normally consumed by mice given unlimited food access. A control group of the same breed of mice matched for age and gender were allowed unlimited feeding. After three months on the diet, tests of learning and memory revealed better cognitive function in the mice that received restricted diets. Examination of the animals' brains revealed a reduction in the loss of neurons and greater brain mass and synaptic density in the restricted animals in comparison with those provided with unrestricted diets. "We not only observed a delay in the onset of neurodegeneration in the calorie-restricted mice, but the animals were spared the learning and memory deficits of mice that did not consume reduced-calorie diets," Dr Tsai reported. The researchers found an increase in the expression of a protein believed to regulate lifespan known as SIRT1 in the hippocampus area of the calorie restricted animals' brains as well as an increase in SIRT1 activity, which is consistent with other studies involving calorie restriction. When a separate group of mice were given a SIRT1-activating compound, benefits similar to those elicited by calorie restriction were observed. "The question now is whether this type of treatment will work in other animal models, whether it's safe for use over time, and whether it only temporarily slows down the progression of neurodegeneration or stops it altogether," Dr Tsai remarked. "There has been great interest in finding compounds that mimic the benefits of caloric restriction that could be used to delay the onset of age-associated problems and/or diseases," commented Luigi Puglielli, MD, PhD, who has participated in research involving calorie restriction and aging at the University of Wisconsin, Madison. "If proven safe for humans, this study suggests such a drug could be used as a preventive tool to delay the onset of neurodegeneration associated with several diseases that affect the aging brain." |
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