Loss of Ensheathing Glia Contributes to Degeneration in the Aging Fly Brain
The brain-resident innate immune cells known as microglia are thought to play an important part in the age-related decline of cognitive function, and rising dysfunction in brain tissue. In the broader population of microglia in mice and humans, an increase in inflammatory behavior is observed, and likely a major cause of issues in the aging brain. Here, however, researchers focus on a subpopulation of microglia in the fly brain called ensheathing glia that become dysfunctional and decline in number with age. These cells act as a sheath for axons, and thus their loss is understandably problematic. Preventing this loss is shown here to improve brain function and longevity in aging flies. Whether analogous processes are important in the equivalent mammalian microglial cells remains to be determined.
Glia have an emergent role in brain aging and disease. In the Drosophila melanogaster brain, ensheathing glia function as phagocytic cells and respond to acute neuronal damage, analogous to mammalian microglia. We previously reported changes in glia composition over the life of ants and fruit flies, including a decline in the relative proportion of ensheathing glia with time. How these changes influence brain health and life expectancy is unknown.
Here, we show that ensheathing glia but not astrocytes decrease in number during Drosophila melanogaster brain aging. The remaining ensheathing glia display dysregulated expression of genes involved in lipid metabolism and apoptosis, which may lead to lipid droplet accumulation, cellular dysfunction, and death. Inhibition of apoptosis rescued the decline of ensheathing glia with age, improved the neuromotor performance of aged flies, and extended lifespan. Furthermore, an expanded ensheathing glia population prevented amyloid-beta accumulation in a fly model of Alzheimer's disease and delayed the premature death of the diseased animals. These findings suggest that ensheathing glia play a vital role in regulating brain health and animal longevity.