Fundamental neurochemistry review: Old brain stories - Influence of age and sex on the neurodegeneration-associated lipid changes

Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age-associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age-related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non-biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age-related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid-related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid-lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid-reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach.

Automated summary

Brain aging leads to cognitive decline and increased vulnerability to age-related disorders. Lipid metabolism plays a crucial role in brain function, and changes in lipid composition have been linked to aging and neurodegenerative diseases. This study focuses on sex differences in brain lipid changes during aging and in Alzheimer's and Parkinson's diseases. The findings highlight the need to consider sex as an experimental variable in precision medicine research.