Comparing the effects of low protein, high carbohydrate diets and caloric restriction on brain aging in mice.

Calorie restriction (CR) increases lifespan and improves brain health in mice. Ad libitum low protein, high carbohydrate (LPHC) diets also extend lifespan, but it is not known whether they are beneficial for brain health. We compared hippocampus biology and memory in mice subjected to 20% CR or provided ad libitum access to one of three LPHC diets, or to a control diet. At age 15 months, patterns of RNA expression in the hippocampus were similar between CR and LPHC diets for genes associated with longevity, cytokines and dendrite morphogenesis. Nutrient sensing proteins including SIRT1, mTOR and PGC1α 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. CR and LPHC diets led to modest improvements in the Barnes Maze and Novel Object Recognition. LPHC diets recapitulate some of the benefits of CR on brain aging. 30 samples, 6 biological replicates in each group.卡路里限制（Calorie Restriction, CR）可延长小鼠寿命并改善其大脑健康状况。自由进食低蛋白高碳水（Low Protein High Carbohydrate, LPHC）饮食同样能够延长小鼠寿命，但目前尚不明确其对大脑健康是否具有益处。本研究对接受20%卡路里限制、自由进食三种低蛋白高碳水饮食中的一种，或喂食对照饮食的小鼠的海马体生物学特征与记忆能力进行了对比分析。当小鼠月龄达到15个月时，在长寿相关基因、细胞因子及树突形态发生相关基因的表达层面，卡路里限制组与低蛋白高碳水饮食组的海马体RNA表达模式较为相似。包括SIRT1、mTOR与PGC1α在内的营养感应蛋白同样会受到饮食干预的影响，但其调控效果存在性别差异。卡路里限制与低蛋白高碳水饮食均可增加齿状回神经元的树突棘数量。两种饮食干预方式均能在巴恩斯迷宫实验与新物体识别实验中使小鼠的记忆能力得到小幅改善。低蛋白高碳水饮食可部分复刻卡路里限制在改善大脑衰老方面的获益效果。本实验共包含30个样本，每组设置6个生物学重复。