The impact of low protein, high carbohydrate diets on brain aging in mice

Devin Wahl

Charles Perkins Centre and ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia

Calorie restriction (CR) is one of the most robust nutritional interventions to improve health and lifespan in most model organisms. There is mounting evidence to suggest that ad-libitum low-protein, high carbohydrate (LPHC) diets are also beneficial to improve health and increase longevity in mice but it is not known whether the same result may hold true for brain aging. To answer this question, we compared the influence of LPHC diets and traditional 20% CR on hippocampus biology and memory in male and female C57/B6 mice. In addition to improving markers of metabolic health, LPHC and CR diets positively influenced hippocampus biology. LPHC and CR diets similarly influenced the expression of genes involved in inflammation, neurite morphogenesis, and longevity. The expression of the main nutrient sensing proteins were also influenced by the diets, however, this result was largely sex dependent. LPHC and CR diets increased hippocampus dendritic spine density and increased memory performance on the Barnes Maze spatial memory test and novel object recognition test. Overall, the results of the current study indicate the LPHC may recapitulate some of the benefits of CR with improving brain health during aging.


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