Ensheathing glia promote increased lifespan and healthy brain aging

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.

Automated summary

By studying the changes in the number and gene expression of ensheathing glia in Drosophila melanogaster brain, it is found that dysregulated ensheathing glia can lead to lipid droplet accumulation, cellular dysfunction, and death, affecting brain health and lifespan. Inhibition of apoptosis can restore the declining number of ensheathing glia with age, improve the neuro-motor performance of aged fruit flies and prolong lifespan. Furthermore, an expanded ensheathing glia population can prevent amyloid-beta accumulation in a fly model of Alzheimer's disease and delay the premature death of diseased animals. These findings highlight the vital role of ensheathing glia in regulating brain health and animal longevity.