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Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans.

Authors
  • Zhang, Yue1
  • Lanjuin, Anne1
  • Chowdhury, Suvagata Roy1
  • Mistry, Meeta1
  • Silva-García, Carlos G1
  • Weir, Heather J1
  • Lee, Chia-Lin1, 2
  • Escoubas, Caroline C1, 3
  • Tabakovic, Emina1
  • Mair, William B1
  • 1 Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States. , (United States)
  • 2 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan. , (Taiwan)
  • 3 Faculty of Medicine, Université Côte d'Azur, CNRS, INSERM, IRCAN, Nice, France. , (France)
Type
Published Article
Journal
eLife
Publisher
"eLife Sciences Organisation, Ltd."
Publication Date
Aug 14, 2019
Volume
8
Identifiers
DOI: 10.7554/eLife.49158
PMID: 31411562
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Target of rapamycin complex 1 (TORC1) and AMP-activated protein kinase (AMPK) antagonistically modulate metabolism and aging. However, how they coordinate to determine longevity and if they act via separable mechanisms is unclear. Here, we show that neuronal AMPK is essential for lifespan extension from TORC1 inhibition, and that TORC1 suppression increases lifespan cell non autonomously via distinct mechanisms from global AMPK activation. Lifespan extension by null mutations in genes encoding raga-1 (RagA) or rsks-1 (S6K) is fully suppressed by neuronal-specific rescues. Loss of RAGA-1 increases lifespan via maintaining mitochondrial fusion. Neuronal RAGA-1 abrogation of raga-1 mutant longevity requires UNC-64/syntaxin, and promotes mitochondrial fission cell nonautonomously. Finally, deleting the mitochondrial fission factor DRP-1 renders the animal refractory to the pro-aging effects of neuronal RAGA-1. Our results highlight a new role for neuronal TORC1 in cell nonautonomous regulation of longevity, and suggest TORC1 in the central nervous system might be targeted to promote healthy aging. © 2019, Zhang et al.

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