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Ensheathing glia promote increased lifespan and healthy brain aging |
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| Authors: | Lihong Sheng Emily J. Shields Janko Gospocic Masato Sorida Linyang Ju China N. Byrns Faith Carranza Shelley L. Berger Nancy Bonini Roberto Bonasio |
| Affiliation: | 1. State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China;2. Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;3. Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Department of Urology and Institute of Neuropathology, Medical Center–University of Freiburg, Freiburg, Germany;4. Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;5. Medical Scientist Training Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA;6. Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA;7. Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;8. Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, USA |
| Abstract: | 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. |
| Keywords: | aging brain drosophila glia |