Which diet is best for the aging brain? Study investigates

Combined with calorie restriction, a low-fat diet may protect the aging brain against inflammation-related activation of microglia, according to a new study of mice.

Microglia are a type of immune cell whose dysfunction has been linked to development problems and diseases of the brain and central nervous system (CNS).

The study — which was led by the University Medical Center Groningen (UMCG) in the Netherlands and published in the journal Frontiers in Molecular Neuroscience — discovered that exercise was far less effective than restricting calorie intake at preventing the inflammatory activation of microglia brought on by aging.

Microglia and aging-induced inflammation

Scientists have found that microglia play an essential role in the development of neurons, or nerve cells, as well as in the transmission of signals between neurons.

We also know that microglia monitor the functional tissues of the brain and the rest of the CNS and react to subtle changes in their microenvironments.

In addition, some studies have shown that microglia play a key role in certain diseases of the CNS.

For example, it has been suggested that through interaction with pro- and anti-inflammatory agents, microglia help to maintain the balance between neuron survival and death in amyotrophic lateral sclerosis, which is a severe disease that affects motor neurons.

We also know that, as we age, some regions of the brain become inflamed because of microglia activity. But what is not clear is how this process responds to diet and lifestyle.

"Obesity and aging," explains senior study author Bart J. Eggen, who is a professor of molecular neuroimmunology at UMCG, "are both prevalent and increasing in societies worldwide, but the consequences for the central nervous system are not well understood."

Low-fat diet and calorie restriction

For their study, Prof. Eggen and his colleagues examined the effect of high-fat and low-fat diets on markers of inflammation and microglia activity in the hypothalami of mice aged 6 months. At this age, mice are adult but not elderly.

They also investigated the impact of high-fat and low-fat diets on the microglia of two groups of elderly 2-year-old mice.

One group had been raised on a lifelong regime of exercise (they could voluntarily use an exercise wheel), while the other had been raised on a lifelong regime of 40 percent calorie restriction but with no exercise.

The findings revealed that only a low-fat diet combined with calorie restriction prevented microglia-driven inflammation brought on by aging.

"A low-fat diet per se was not sufficient to prevent these changes," Prof. Eggen observes.

Exercise less effective than calorie restriction

The researchers also found that exercise was far less effective at preventing these aging-related changes than calorie restriction.

This is in contrast to findings by other groups that suggest that exercise might reduce the risk of developing other diseases.

The study authors point out that there are still many questions to be answered before we can understand what these findings mean.

Take, for example, the fact that the mice were only fed one type of diet for their whole lives. This means that the findings cannot address questions about changes in diet.

And, could a low-fat diet with calorie restriction undo any potential damage that might be inflicted by a high-fat, unrestricted diet? And, if so, how early in life should the switch take place for the consequences to be significant?

Also, further work is needed to establish the extent to which these changes are related to changes in cognitive performance.

"Nevertheless," Prof. Eggen concludes, "these data do show that, in mice, the fat content of a diet is an important parameter in terms of the detrimental effects of aging on the brain, as well as caloric intake."

"Only when fat content and caloric intake are limited, can aging-induced changes in microglia be prevented."