Comparing the Effects of Low-Protein and High-Carbohydrate Diets and Caloric Restriction on Brain Aging in Mice

Devin Wahl,David Sinclair,David Le Couteur,Stephen Simpson,Samantha Solon-Biet,David Raubenheimer,Rafael De Cabo

doi:10.1093/geroni/igaa057.3103

Abstract

The Geometric Framework for Nutrition (GFN) has revealed that ad-libitum low-protein, high-carbohydrate (LPHC) diets improve cardiometabolic health and extend lifespan in rodents, but it is not known whether these diets are also beneficial for brain health. Here, we utilized previous results from GFN studies and compared hippocampus biology and memory in mice subjected to 20% calorie restriction (CR) or provided ad-libitum access to several LPHC diets. RNA expression in the hippocampus of 15-month-old mice were similar between mice fed CR and LPHC diets. Nutrient-sensing proteins, including SIRT1, MTOR, and PGC1-alpha, were also influenced by diet; however, the effects varied by sex. CR and LPHC diets were associated with increased dendritic spines in dentate gyrus neurons. Mice fed CR and LPHC diets had modest improvements in the Barnes maze spatial recognition memory paradigm and novel object recognition test. LPHC diets recapitulate some of the benefits of CR on brain aging. Part of a symposium sponsored by the Nutrition Interest Group.

Highlights

Nutritional interventions, such as caloric restriction (CR), influence aging and age-related changes in the brain (Mattson et al, 2018; Wahl et al, 2016)
These diets had no significant effect on insulin-like growth factor 1 (IGF-1) (Figure 1I), whereas cholesterol was highest on the 10% protein diet and lowest with CR (Figure 1L)
CR diets and LPHC diets were associated with modest improvements in behavioral and cognitive outcomes, the results were mainly limited to females and inconsistent

Summary

Introduction

Nutritional interventions, such as caloric restriction (CR), influence aging and age-related changes in the brain (Mattson et al, 2018; Wahl et al, 2016). CR improves cognitive function, including learning and memory, in old rodents (Ingram et al, 1987; Wahl et al, 2017), possibly mediated by its effects on cardiometabolic risk factors, generic hallmarks of aging, specific brain-related mechanisms (BDNF, neurogenesis) or nutrient-sensing pathways (Wahl et al, 2016). Mice consuming a low-protein, highcarbohydrate, low-fat diet (LPHC, protein:carbohydrate ~1:10) lived longest and were healthier in old age, even when compared to CR achieved by dilution of chow with nondigestible fiber (Solon-Biet et al, 2014). The beneficial effects of LPHC diets on lifespan are conserved across a range of organisms from invertebrates to mice (Le Couteur et al, 2016)

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Discussion

Conclusion