Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), E-25198 Lleida, Spain.
Institut Català de la Salut, Atenció Primària, E-25007 Lleida, Spain.
Int J Mol Sci. 2021 Nov 20;22(22):12517. doi: 10.3390/ijms222212517.
Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)-as an anti-aging intervention-for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.
脂质与大脑结构和功能密切相关。然而，衰老引起的脂质组学的潜在变化仍有待阐明。在这项研究中，我们使用色谱技术和基于质谱的方法来评估来自成年雄性 Wistar 大鼠（8 个月）、老年雄性 Wistar 大鼠（26 个月）和接受蛋氨酸限制饮食（MetR）的老年雄性 Wistar 大鼠（作为抗衰老干预措施）的 8 周）的前额叶皮层和小脑的脂质组学变化。结果表明，在衰老过程中，小脑和前额叶皮层的脂质组学图谱仅发生了约 10%的微小变化，并且这些变化在某些情况下在不同区域之间存在差异。此外，MetR 饮食部分逆转了衰老过程的影响。值得注意的是，受影响最大的脂质类是醚三酰甘油、二酰甘油、磷酸乙醇胺 N-甲基化、血浆类脂、神经酰胺和胆固醇酯。当分析脂肪酸图谱时，我们观察到前额叶皮层在衰老过程中高度保存，并在 MetR 下保持，而小脑则观察到较小的变化（单不饱和脂肪酸增加和多不饱和脂肪酸减少），并且 MetR 无法逆转。我们得出结论，大鼠小脑和前额叶皮层具有有效的机制来维持其细胞膜的脂质谱，以维持大脑结构和功能。衰老过程中发生的一小部分变化可以通过老年时应用 MetR 饮食来逆转。
