A class of anti-inflammatory lipids decrease with aging in the central nervous system

Lipids contribute to the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to aging and diseased brains. However, our understanding of lipid metabolism in aging brains remains limited. Here we examined the brain lipidome of mice across their lifespan using untargeted lipidomics. Co-expression network analysis highlighted a progressive decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) and SGDG pathway members, including the potential degradation products lyso-SGDGs. SGDGs show an age-related decline specifically in the central nervous system and are associated with myelination. We also found that an SGDG dramatically suppresses LPS-induced gene expression and release of pro-inflammatory cytokines from macrophages and microglia by acting on the NF-kappa B pathway. The detection of SGDGs in human and macaque brains establishes their evolutionary conservation. This work enhances interest in SGDGs regarding their roles in aging and inflammatory diseases and highlights the complexity of the brain lipidome and potential biological functions in aging.

Automated summary

Lipids play important roles in the structure, development, and function of healthy brains. Dysregulated lipid metabolism is linked to diseased brains. This study examined the brain lipidome of mice and found a decrease in 3-sulfogalactosyl diacylglycerols (SGDGs) in the central nervous system with aging, which is associated with myelination. Additionally, SGDG was found to suppress inflammation by acting on the NF-kappa B pathway.