Drug Replicates Anti-Aging Benefits Of Lower-Calorie Diets In Mice

Reduced Calories Impacted Enzyme Associated With Aging, In Mice
A low-calorie diet in mice impacted an enzyme known to affect aging, in a study of mice. Creative Commons

As high-income countries face health problems related to diets that emphasize quantity over quality, investigators confirm that lower-calorie diets slow the aging of the brain across a variety of species, with the possible benefit of extending the human lifespan.

Investigators from MIT reported last week that mice fed a low-calorie diet experienced slower mental decline as they aged. Past research showed that reduced caloric intake abates cognitive decline associated with aging and neurodegenerative diseases such as Alzheimer's. Evidence connects calorie restrictions with the activation of the sirtuin 1 enzyme, a regulatory enzyme related to longevity and reactions to stress.

In this study, researchers discovered that calorie restriction slows the loss of nerve cells in the brain and replicated the effect with a drug that activated the enzyme.

"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," Dr. Luigi Puglielli, who studies aging at the University of Wisconsin, Madison, said. "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."

Li-Huei Tsai, director of the Picower Institute for Learning and Memory and Picower at MIT led the study, which was published Wednesday in the The Journal of Neuroscience. She and her team fed a diet 30 percent lower in calories than normal to mice genetically engineered to rapidly undergo changes in the brain associated with neurodegeneration.

"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 said.

Most important, the researchers found they could replicate the benefits of calorie restriction without changing the diets, using a drug shown to activate the SIRT1 enzyme. Those mice, too, experienced a slower rate of cell loss with better cellular connectivity than mice that received neither lower-calorie diets nor the drug. They also performed as well as other 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.

The research was supported by the U.S. National Institute on Aging and the Swiss National Science Foundation.

 

Source: Gräff J, Alireza S, Jun G, et al. A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration. The Journal of Neuroscience. 2013.

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