Calorie restriction may not slow memory loss, finds mice study

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Related tags: Senescence

Severe calorie restriction prevents certain ageing-related changes
in the brain, including the accumulation of free radicals and
impairments in coordination and strength, according to a mouse
study.

However, the dietary changes did not seem to prevent mice from developing some cognitive deficits associated with age, such as declines in memory, reported researchers from Washington University School of Medicine at a conference this weekend.

Though numerous studies have shown severe calorie restriction helps animals live longer and resist some effects of ageing, scientists still do not know why. One theory suggests a restrictive diet decreases the effect of free radical damage. Scientists think accumulating too many free radicals may cause cell damage and contribute to a variety of diseases ranging from stroke to cancer.

Since there is evidence that both antioxidants - which help prevent the damage done by free radicals - and calorie restriction increase lifespan and reduce aging-related diseases, principal investigator Dr Laura L. Dugan and colleagues hypothesized that calorie restriction, like antioxidants, may help protect the brain against free radical damage.

"If some aspects of ageing are influenced by free radical damage, we may be able to prevent or reverse these impairments,"​ said Dugan.

To test their theory, the team compared young and old mice fed normal diets with old mice fed 35 per cent fewer calories starting at about one year old. One year for mice is roughly the physiological equivalent of 40 years in humans.

Old mice fed normal diets had significantly more superoxide - a free radical - in several regions of the brain than their young counterparts, particularly in one region implicated in Parkinson's disease, called the substantia nigra. But calorie-restricted old mice did not.

"For the last 20 years there have been studies that suggest free radicals, particularly superoxide, are involved in cumulative damage with ageing and that the nervous system may be one of the most vulnerable targets,"​ Dugan said.

"Most of that evidence has been indirect, though. By using sensitive, state-of-the-art methods, we were actually able to see which cells are producing excess levels of free radicals."

Dugan and her colleagues then evaluated animals that retained low levels of superoxide to see if they maintained their ability to do a range of behavioural tasks. They found that old, calorie-restricted animals were just as good as young animals at tests of grip strength, coordination and flexibility, like quickly climbing down a pole and hanging upside down from a screen. Old animals fed normal diets were significantly worse at these tasks.

But calorie restriction had almost no effect on several drills used to measure pure cognitive performance. In one test of spatial learning and memory called the Morris water maze, old mice, regardless of their diet, performed much worse than young mice.

Calorie restriction also did not result in improved performance on a fear-conditioning task. In fact, the researchers noticed a trend that suggests mice on calorie restriction diets were even worse than old mice on normal diets. The researchers are not sure though, whether this poor performance is a sign of learning deficits or of hearing problems that often develop in older mice.

David Wozniak, Ph.D., research associate professor of psychiatry, who supervised the behavioral studies, said: "We need to do bigger, more extensive studies to fully understand these findings, but the bottom line is that you don't get uniformly positive results from calorie restriction. I don't think anyone has really stressed this point before, particularly with regard to the lack of effects on cognition."

The team is now looking to validate these findings in larger groups of mice and also exploring the possibility that adjusting other dietary factors may enhance and add to the calorie restriction diet's benefits.

The researchers also have begun testing the protective effects of potent antioxidants on ageing mice fed normal diets to see whether they too can prevent or reverse some of the effects of ageing.

"We believe sensitive signaling pathways that are particularly important in the brain are disrupted by high levels of free radicals and that these disruptions may explain why, under normal circumstances, brain function declines over time,"​ Dugan said. "Fortunately, it would be much easier to reverse a misregulation in signaling than it would to reverse cell damage."

The research was presented yesterday at Neuroscience 2004​ in San Diego.

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