@article{2ccb360090774df5886a2d050288a1dc,
title = "Ensheathing glia promote increased lifespan and healthy brain aging",
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",
author = "Lihong Sheng and Shields, {Emily J.} and Janko Gospocic and Masato Sorida and Linyang Ju and Byrns, {China N.} and Faith Carranza and Berger, {Shelley L.} and Nancy Bonini and Roberto Bonasio",
note = "Funding Information: The authors thank A. Seghal for the generous gift of Iso31 strain and for providing the LSD2::GFP flies. We are grateful to M. Welte for allowing to use the LSD2::GFP flies generated in his laboratory. L.S. was supported in part by grants from National Natural Science Foundation of China (programs 32100782 and 32271018), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01), ZJ Lab, and Shanghai Center for Brain Science and Brain‐Inspired Technology. Work in the Bonasio laboratory was supported by the NIH (R01AG071818, R21MH123841, and R01MH131861). Work in the Bonini laboratory was supported by F31‐NS111868 (to C.N.B.) and R35‐NS097275 (to N.M.B.). Work in the Berger laboratory was supported by the NIH (R01AG55570). Funding Information: The authors thank A. Seghal for the generous gift of Iso31 strain and for providing the LSD2::GFP flies. We are grateful to M. Welte for allowing to use the LSD2::GFP flies generated in his laboratory. L.S. was supported in part by grants from National Natural Science Foundation of China (programs 32100782 and 32271018), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01), ZJ Lab, and Shanghai Center for Brain Science and Brain-Inspired Technology. Work in the Bonasio laboratory was supported by the NIH (R01AG071818, R21MH123841, and R01MH131861). Work in the Bonini laboratory was supported by F31-NS111868 (to C.N.B.) and R35-NS097275 (to N.M.B.). Work in the Berger laboratory was supported by the NIH (R01AG55570). Publisher Copyright: {\textcopyright} 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.",
year = "2023",
month = may,
doi = "10.1111/acel.13803",
language = "English (US)",
volume = "22",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "5",
}