Lifespan regulation in α/β posterior neurons of the fly mushroom bodies by Rab27

Wen Yu Lien, Yu Ting Chen, Yi Jhan Li, Jie Kai Wu, Kuan Lin Huang, Jian Rong Lin, Shih Ching Lin, Chia Chun Hou, Horng Dar Wang, Chia Lin Wu, Shu Yi Huang, Chih Chiang Chan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

Brain function has been implicated to control the aging process and modulate lifespan. However, continuous efforts remain for the identification of the minimal sufficient brain region and the underlying mechanism for neuronal regulation of longevity. Here, we show that the Drosophila lifespan is modulated by rab27 functioning in a small subset of neurons of the mushroom bodies (MB), a brain structure that shares analogous functions with mammalian hippocampus and hypothalamus. Depleting rab27 in the α/βp neurons of the MB is sufficient to extend lifespan, enhance systemic stress responses, and alter energy homeostasis, all without trade-offs in major life functions. Within the α/βp neurons, rab27KO causes the mislocalization of phosphorylated S6K thus attenuates TOR signaling, resulting in decreased protein synthesis and reduced neuronal activity. Consistently, expression of dominant-negative S6K in the α/βp neurons increases lifespan. Furthermore, the expression of phospho-mimetic S6 in α/βp neurons of rab27KO rescued local protein synthesis and reversed lifespan extension. These findings demonstrate that inhibiting TOR-mediated protein synthesis in α/βp neurons is sufficient to promote longevity.

Original languageEnglish
Article numbere13179
JournalAging Cell
Volume19
Issue number8
DOIs
StatePublished - 01 08 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Keywords

  • Drosophila
  • Rab27
  • S6K
  • TOR
  • lifespan extension
  • mushroom body

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