Abstract

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.

Highlights

  • The abundance and diversity of lipid classes and molecular species present in the nervous system of animal species is evidence of the relevance of this family of compounds for the structure and function of neural cells [1,2]

  • Our global lipidome analysis detected a total of 13,949 molecular features from both ionization modes once baseline correction, peak picking, and peak alignment were applied on acquired data

  • There is a lack of studies analyzing the effects of aging and anti-aging interventions applied in old age on lipid composition in distinct regions of the rat brain, and using a lipidomics approach

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Summary

Introduction

The abundance and diversity of lipid classes and molecular species present in the nervous system of animal species is evidence of the relevance of this family of compounds for the structure and function of neural cells [1,2]. Previous studies on rat brains suggested age-related changes of individual lipid classes such as sterols [14], glycerophospholipids [15,16,17], and gangliosides [17,18] in the whole brain [18] or specific brain regions such as the amygdala, cerebral cortex, cerebellum, frontal cortex, hippocampus, and hypothalamus [14,15,16,17,19]. Most of these studies involved a partial analysis of the lipidome, focusing on specific lipid categories or classes

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