The supporting cells of the brain are collectively known as glia. This category includes astrocytes, microglia, and oligodendrocytes, among others, cells that are responsible for maintenance of an environment in which neurons can function, or directly aiding neuron function in various ways. Researchers here discuss how age-related changes in the interactions between neurons and glia may both arise from neurodegeneration and drive neurodegeneration. Manipulating some of these interactions can slow aging and extend life span in flies.
Aging is often discussed as something that happens inside cells: DNA is damaged, mitochondria stop working, and proteins are misfolded. But aging also changes how cells communicate with each other. For example, neurons in the brain rely on neighboring cells, called glia, for nutrients, waste handling, and local repair. Dysregulation of the interactions between neuron and glia is considered a hallmark of brain aging, but the consequences of disrupting neuron-glia communications are still being uncovered.
Researchers compared glial cell-surface proteomes in young (5 day) and old (50 day) flies to examine how signaling molecules are regulated in the aging brain, and identified a set of 872 proteins that exhibited age-specific differences in abundance. Proteins that became more abundant with age were enriched for functions related to localization and transport, which supports the idea that older brains may need stronger homeostasis and trafficking control. In contrast, many proteins that became less abundant with age were associated with synapse organization, axon guidance, and related processes.
The researchers chose 48 genes that exhibited the greatest changes between the glial surface proteomes of young and old flies, and tested whether manipulating these genes in adult glia altered lifespan. One candidate from the screen, a cell adhesion protein called DIP-β, was found to extend lifespan in both males and females when overexpressed in glia. Older flies with higher levels of DIP-β in their glia also climbed better than controls, suggesting improved late-life function in addition to longer lifespan. Analysis suggested that DIP-β overexpression was associated with increased signaling between glia and neurons, and between glia and fat cells, with prominent shifts in a number of signaling pathways (such as the TGF-beta, Wnt, FGFR, and EGFR pathways). This is an appealing model because it connects a surface protein found in glia to broader tissue coordination during aging.
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