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

Activation of SIRT1 through calorie restriction or drug treatment delays neurodegeneration in experimental model
Photo courtesy of Li-Huei Tsai, PhD

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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Berries improve neuronal housekeeping

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In an abstract summarizing the results of a study reported at the Experimental Biology 2013 meeting, published on April 9, 2013 in The FASEB Journal, researchers from Tufts University report a benefit for strawberry and blueberry consumption in improving autophagy in the brain. Autophagy is a process employed by the body to clear the accumulation of unnecessary or damaged cellular components that have been implicated in some disorders. "Most diseases of the brain such as Alzheimer's and Parkinson's have shown an increased amount of toxic protein," explained research team member Shibu Poulose, PhD, of Tufts' Human Nutrition Research Center on Aging. "Berries seem to promote autophagy, the brain's natural housekeeping mechanism, thereby reducing the toxic accumulation."

In a study led by Dr Barbara Shukitt-Hale, rats were provided with a control diet or a diet supplemented with strawberries or blueberries for two months prior to and 30 days following irradiation of the brain (which results in oxidative and inflammatory stress to that organ). Some of the animals underwent examination of their brains 36 hours following irradiation and the remaining animals were examined after 30 days.

The team observed a reduction in inflammation and oxidative stress in rats that received diets enhanced with either berry, as well as improved indicators of autophagy activation in comparison with untreated animals. "After 30 days on the same berry diet, the rats experienced significant protection against radiation compared to control," Dr Poulose reported. "We saw significant benefits to diets with both of the berries, and speculate it is due to the phytonutrients present."

"We have a lot of animal work that suggests these compounds will protect the aged brain and reverse some of behavioral deficits," stated Dr Shukitt-Hale. "We are hoping it will translate to human studies as well."

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