Cut the calories to keep the brain healthy?

Related tags Senescence

People who restrict their calorie intake may not only prevent
cardiovascular disease and cancer, but could also protect their
mental health, say researchers in the US, who claim they have found
significant results in a study on calorie-restricted rats.

Those seeking to cut down on calories in the New Year may also be protecting the brain from ageing, according to researchers at the University of Florida.

The team found that certain proteins linked to cell death which naturally increase with age were significantly reduced in the brains of rats whose calories were limited.The researchers claim this is the first study to look specifically at the effects of life-long calorie-restricted diets on brain cells.

They also report that levels of a beneficial protein known to provide strong protection against neuron death were twice as high in older rats whose calories were restricted by 40 per cent.

The scientists say their findings could have significant implications not only for alleviating memory loss and other effects that accompany normal ageing, but also for a host of disorders related to excessive loss of brain cells, such as Alzheimer's and Parkinson's diseases.

"In normal ageing, there's a variety of factors that could alter the internal environment of the cell and make it more prone to die. We would like to stop this,"​ said Christiaan Leeuwenburgh, director of the Biochemistry of Aging Laboratory at UF's College of Health and Human Performance. "Cells in neurons, muscle and heart have very low regenerative capacity, so obviously you don't want to lose a lot of them."

As ageing progresses, neurons of the brain and central nervous system are thought to be increasingly susceptible to apoptosis, a genetically programmed series of events leading to cell death. Apoptosis can occur as a normal process to destroy old cells so new ones can be made, or due to disease, infection, damaged DNA or other illnesses.

Based on decades of research in several species, the results show that calorie restriction not only boosted life span and general health but also increased mental capacity. Leeuwenburgh and his colleagues also set out to determine if cutting calories protected ageing neurons.

Understanding the reasons calorie restriction increases certain neuroprotective proteins is important so that some day researchers may be able to develop therapies to repair cells harmed in the disease process or target genes to release additional amounts of these proteins to ensure healthy life, said Leeuwenburgh.

Mitochondria - the cells' energy-producing centres - can be damaged by free radicals or through calcium imbalances and other processes during normal aging or as a result of disease. When that happens they release proteins, most notably cytochrome c, that initiate cell death.

Using standard tests, Leeuwenburgh measured the levels of cytochrome c and other indicators of apoptosis in the cytosolic fraction of the frontal cortexes - areas important in learning and memory - of three groups of rats: 12- and 26-month-old animals given unlimited food and water, and a group of 26-month-old rats given 40 per cent fewer calories than those in the unrestricted groups. The animals in the last group received food that was more nutritionally dense to ensure they were not malnourished, a key concern about calorie-restricted diets, Leeuwenburgh said.

The researchers found that cytochrome c, a natural protein that is harmless until mitochondria becomes damaged, increased with age in the normally nourished animals. In the 26-month-old, calorie-restricted rats, however, the protein did not increase; instead, it remained at the level of the young rats.

The researchers focused on a novel protein - ARC, or apoptosis repressor with a caspase recruitment domain. They discovered that while this beneficial protein, known to prevent the release of cytochrome c and other destructive substances, dropped 60 per cent with age in the freely fed rats, levels of it increased over time in the older calorie-restricted animals. These rats showed 40 per cent more ARC than in the young animals and 80 per cent more than the older unrestricted animals.

The study also found that specific DNA fragmentation, another indicator of apoptosis, more than doubled in the unrestricted animals over time, but were 36 per cent less in the calorie-restricted rats.

Additional proteins called tumour necrosis factor and caspases 2 and 8 - dormant proteins that become destructive when activated by the onset of apoptosis - also increased with age in the normally fed animals but were relatively unchanged in those that had been restricted, the researchers found.

In the future, Leeuwenburgh will explore other pathways that may play roles in neuron death. He added that while there are still many questions and major Western lifestyle obstacles to overcome, calorie restriction provides significant health benefits, even if started later in life.

"We're not going to do it right away to improve our memories; we're going to do it probably in general for the first reasons, which would be to prevent cardiovascular disease and cancer. But maybe it also has a protective effect - and it's very suggestive in this study that it does - on brain function."

Mark Mattson, chief of the National Institute on Aging's neurosciences laboratory, said: "The authors have made a new and potentially important finding concerning the mechanism whereby caloric restriction retards the aging process. If their discovery is valid, the authors' finding reveals a novel ageing pathway that could be targeted by other dietary manipulations or drugs."

The study, supported by grants from the US National Institutes of Health and the National Institute of Aging, is published in the recent online edition of the journal of the Federation of American Societies for Experimental Biology.

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