Aging membranes: Unexplored functions for lipids in the lifespan of the central nervous system

Lipids constitute a significant group of biological metabolites and the building blocks of all cell membranes. The abundance and stoichiometries of different lipid species are known to vary across the lifespan and metabolic state, yet the functional effects of these changes have been challenging to understand. Here we review the potentially powerful intersection of lipid metabolism, which determines membrane composition, and aging. We first introduce several key lipid classes that are associated with aging and aging-related disease, where they are found in organisms, and how they act on membrane structure and function. Instead of neutral lipids, which have primary roles in energy storage and homeostasis, we review known functions for polar lipids that control the physicochemical properties of cell membranes. We then focus on aging processes in the central nervous system (CNS), which is enriched in lipids and is highly dependent on membrane structure for function. Recent studies show how lipids act not just as biomarkers of aging and associated changes in the CNS, but as direct mediators of these processes. As a model system, we explore how fatty acid composition in the retina impact aging and agingrelated disease. We propose that the biophysical effects of membrane structure on fundamental eukaryotic processes - mitochondrial respiration and autophagy - provide avenues by which lipid dysregulation can accelerate aging processes. Finally, we lay out ways in which an increased understanding of lipid membrane biology can be applied to studies of aging and lifespan.