Sunday, January 11, 2015

Calorie-Restricted Diets Preserve Age AND Memory

Important research provides 2 of the best motivators to watch calories: preserving youth and brains. The research may also hold the key to reducing calories while skipping over the pain of dieting. Find out more.

Neuroscientists at NYU Langone Medical Center have shown that calorie-reduced diets stop the normal rise and fall in activity levels of close to 900 different genes linked to aging and memory formation in the brain.

In a presentation prepared for the Society for Neuroscience annual meeting in Washington, D.C., on Nov. 17, researchers say their experimental results, conducted in female mice, suggest how diets with fewer calories derived from carbohydrates likely deter some aspects of aging and chronic diseases in mammals, including humans.

Gene Expression & Calorie Restriction

"Our study shows how calorie restriction practically arrests gene expression levels involved in the aging phenotype -- how some genes determine the behavior of mice, people, and other mammals as they get old," says senior study investigator and NYU Langone neuroscientist, Stephen D. Ginsberg, PhD. Ginsberg cautions that the study does not mean calorie restriction is the "fountain of youth," but that it does "add evidence for the role of diet in delaying the effects of aging and age-related disease."

While restrictive dietary regimens have been well-known for decades to prolong the lives of rodents and other mammals, their effects in humans have not been well understood. Benefits of these diets have been touted to include reduced risk of human heart disease, hypertension, and stroke, Ginsberg notes, but the widespread genetic impact on the memory and learning regions of aging brains has not before been shown. Previous studies, he notes, have only assessed the dietary impact on one or two genes at a time, but his analysis encompassed more than 10,000 genes.

Ginsberg, an associate professor at NYU Langone and its affiliated Nathan S. Kline Institute for Psychiatric Research, says the research "widens the door to further study into calorie restriction and anti-aging genetics."

For the study, female mice, which like people are more prone to dementia than males, were fed food pellets that had 30 percent fewer calories than those fed to other mice. Tissue analyses of the hippocampal region, an area of the brain affected earliest in Alzheimer's disease, were performed on mice in middle and late adulthood to assess any difference in gene expression over time.

Funding support for the study was provided primarily by the US National Institutes of Health. Corresponding federal grant numbers are RR029893, TR000038, GM007238, R01 AG043375, P01 AG014449, and P01 AG017617. Additional funding support was provided by Alzheimer's Association grant IIRG-12-237253.

Besides Ginsberg, other NYU Langone researchers involved in these experiments were lead study investigator Marissa Schafer, PhD; and co-investigators Igor Dolgalev, MS, and Adriana Heguy, PhD.

Sirt1 is the Key

There is also evidence that caloric restriction activates an enzyme called Sirtuin 1 (SIRT1), which studies suggest offers some protection against age-associated impairments in the brain.

Li-Huei Tsai, PhD, Johannes Gräff, PhD, and others at the Picower Institute For Learning and Memory, Massachusetts Institute of Technology, and Howard Hughes Medical Institute, tested whether reducing caloric intake would delay the onset of nerve cell loss that is common in neurodegenerative disease, and if so, whether SIRT1 activation was driving this effect. The group not only confirmed that caloric restriction delays nerve cell loss, but also found that a drug that activates SIRT1 produces the same effects.

"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," said Luigi Puglielli, MD, PhD, who studies aging at the University of Wisconsin, Madison, and was not involved in this study. "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," Puglielli added.

In the study, Tsai's team first decreased by 30 percent the normal diets of mice genetically engineered to rapidly undergo changes in the brain associated with neurodegeneration. Following three months on the diet, the mice completed several learning and memory tests. "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," Tsai explained.

Curious if they could recreate the benefits of caloric restriction without changing the animals' diets, the scientists gave a separate group of mice a drug that activates SIRT1. Similar to what the researchers found in the mice exposed to reduced-calorie diets, the mice that received the drug had less cell loss and better cellular connectivity than the mice that did not receive the drug. Additionally, the mice that received the drug treatment performed as well as normal mice in learning and memory tests.

"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," Tsai said.

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