This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

这项体内研究旨在测试富含 6% 核桃的饮食是否可以通过改变大脑和肝脏中的 oxylipin 谱、改善运动功能、认知和大脑线粒体功能来支持健康老龄化。雌性 NMRI 小鼠从 12 个月大时开始喂食 6% 的核桃饮食，持续 24 周。一组另外维持在丰富的环境中，一组没有干预作为对照。三个月后，引入了一组额外的年轻小鼠（3 周大）对照组。使用 Open Field、Y-Maze、Rotarod 和被动回避测试测量运动和认知功能。使用 RP-LC-ESI(-)-MS/MS 在小鼠的脑和肝组织中测定脂质代谢物谱。脑线粒体功能的特征在于 ATP 水平的测定，线粒体膜电位和线粒体呼吸。使用 qRT-PCR 确定与有丝分裂和神经发生、炎症和突触可塑性有关的基因的表达。在小鼠的 Y 迷宫交替测试 (p < 0.05) 中，单独的 6% 富含核桃的饮食改善了空间记忆。额外的身体充实增强了重要性，尽管总体益处几乎相同。相反，在 Rotarod 实验中，身体丰容改善了运动表现（尽管总体收益几乎相同。相反，在 Rotarod 实验中，身体丰容改善了运动表现（尽管总体收益几乎相同。相反，在 Rotarod 实验中，身体丰容改善了运动表现（p * < 0.05) 不受单独核桃的影响。与对照小鼠相比，来自亚油酸 (LA) 的羟基多不饱和脂肪酸 (OH-PUFA) 等生物活性氧脂在大脑 ( p ** < 0.01) 和肝脏 ( p *** < 0.0001)中显着增加，而 OH- α-亚麻酸 (ALA) 的 PUFA 只能在喂食核桃的小鼠大脑中检测到。在大脑中，核桃与体力活动相结合降低了基于花生四烯酸 (ARA) 的氧脂水平 ( p < 0.05)。核桃脂质的影响与线粒体功能无关，因为 ATP 产生、线粒体膜电位和线粒体呼吸不受影响。此外，突触可塑性和神经元生长的常见标志物、调节细胞保护反应对氧化应激和神经元生长的关键基因不受影响。总之，核桃会改变肝脏和大脑中的氧脂素分布，这可能对健康老龄化产生有益影响，这种影响可以通过积极的生活方式进一步增强。进一步的研究可能侧重于可能对大脑提供预防作用的特定营养脂质。