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PLoS Biol. 2017 Sep 13;15(9):e2001655. doi: 10.1371/journal.pbio.2001655. eCollection 2017 Sep.

Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies.

Author information

1
Max Planck Institute for Biology of Aging, Köln, Germany.
2
Institute of Healthy Aging, and Genetics, Evolution, and Environment, University College London, London, United Kingdom.
3
Department of Structural and Molecular Biology, London, United Kingdom.
4
School of Biosciences, University of Kent, Canterbury, Kent, United Kingdom.
5
Department of Biological Sciences, Florida Atlantic University, Jupiter, Florida, United States of America.

Abstract

Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the "insulin paradox"). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced. Furthermore, increasing the activity of the recycling small guanosine triphosphatases (GTPases) Rab4 or Rab11 was sufficient to maintain GJs upon elevated IIS in cultured human cells and in flies, and to rescue age-related loss of GJs and of GFS function. Lowered IIS thus elevates endosomal recycling of GJs in neurons and other cell types, pointing to a cellular mechanism for therapeutic intervention into aging-related neuronal disorders.

PMID:
28902870
PMCID:
PMC5597081
DOI:
10.1371/journal.pbio.2001655
[Indexed for MEDLINE]
Free PMC Article

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