Why eating less may keep the brain young

February, 2012

Two animal studies add to our understanding of why calorie restriction might help prevent cognitive impairment and dementia and how to accrue cognitive benefits from it. A human study adds to the evidence for the benefits of eating less.

I have reported often on studies pointing to obesity as increasing your risk of developing dementia, and on the smaller evidence that calorie restriction may help fight age-related cognitive decline and dementia (and help you live longer). A new mouse study helps explain why eating less might help the brain.

It turns out that a molecule called CREB-1 is triggered by calorie restriction (defined as only 70% of normal consumption). cAMP Response Element Binding (CREB) protein is an essential component of long-term memory formation, and abnormalities in the expression of CREB have been reported in the brains of Alzheimer’s patients. Restoring CREB to Alzheimer’s mice has been shown to improve learning and memory impairment.

Animal models have also indicated a role for CREB in the improvements in learning and memory brought about by physical exercise. CREB seems to be vital for adult neurogenesis.

The current study found that, when CREB1 was missing (in mice genetically engineered to lack this molecule), calorie restriction had no cognitive benefits. CREB deficiency in turn drastically reduced the expression of Sirt-1. These proteins have been implicated in cardiac function, DNA repair and genomic stability (hence the connection to longevity). More recently, Sirt-1 has also been found to modulate synaptic plasticity and memory formation — an effect mediated by CREB. This role in regulating normal brain function appears to be quite separate from its cell survival functions.

The findings identify a target for drugs that could produce the same cognitive (and longevity) benefits without the need for such strict food reduction.

Reducing your eating and drinking to 70% of normal intake is a severe reduction. Recently, researchers at the National Institute on Ageing in Baltimore have suggested that the best way to cut calories to achieve cognitive benefits was to virtually fast (down to around 500 calories) for two days a week, while eating as much as you want on the other days. Their animal experiments indicate that timing is a crucial element if cognitive benefits are to accrue.

Another preliminary report, this time from the long-running Mayo Clinic study of aging, adds to the evidence that lower consumption reduces the risk of serious cognitive impairment. The first analysis of data has revealed that the risk of developing mild cognitive impairment more than doubled for those in the highest food consumption group (daily calorie consumption between 2,143 and 6,000) compared to those in the lowest (between 600 and 1,526 calories).

Calorie consumption was taken from food questionnaires in which respondents described their diets over the previous year, so must be taken with a grain of salt. Additionally, the analysis didn’t take into account types of food and beverages, or other lifestyle factors, such as exercise. Further analysis will investigate these matters in more depth.

The study involved 1,233 older adults, aged 70 to 89. Of these, 163 were found to have MCI.

None of this should be taken as a recommendation for severely restricting your diet. Certainly such behavior should not be undertaken without the approval of your doctor, but in any case, calorie restriction is only part of a much more complex issue concerning diet. I look forward to hearing more from the Mayo Clinic study regarding types of foods and interacting factors.

Reference: 

[2681] Fusco, S., Ripoli C., Podda M V., Ranieri S C., Leone L., Toietta G., et al.
(2012).  A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction.
Proceedings of the National Academy of Sciences. 109(2), 621 - 626.

The findings from the National Institute on Aging were presented at the annual meeting of the American Association for the Advancement of Science in Vancouver.

Geda, Y., Ragossnig, M., Roberts, L.K., Roberts, R., Pankratz, V., Christianson, T., Mielke, M., Boeve, B., Tangalos, E. & Petersen, R. 2012. Caloric Intake, Aging, and Mild Cognitive Impairment: A Population-Based Study. To be presented April 25 at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

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