Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

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Xingyi Cheng1, Meng Xie1, Lu Luo2

  • 1Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, China.

Mechanisms of Ageing and Development
|January 22, 2022
PubMed

Insights

An AKT inhibitor, GSK690693, extends lifespan in fruit flies by improving healthspan markers like oxidative resistance and gut integrity. This compound shows potential as an anti-aging intervention without causing hyperglycemia.

Area of Science:

  • Gerontology and molecular biology
  • Focus on aging processes and molecular pathways

Background:

  • Aging leads to biological function decline, necessitating anti-aging interventions.
  • The PI3K-AKT signaling pathway is a key target in aging research.

Purpose of the Study:

  • To investigate the anti-aging potential of the AKT inhibitor GSK690693.
  • To determine the effects of GSK690693 on lifespan and healthspan in Drosophila.

Main Methods:

  • Administered GSK690693 to Drosophila at different life stages.
  • Assessed lifespan, oxidative resistance, intestinal integrity, autophagy, physical activity, and starvation resistance.
  • Analyzed molecular pathways including AKT, ERK, FOXO, GSK-3β, and apoptosis.

Main Results:

  • GSK690693 significantly extended lifespan in Drosophila.
  • Lifespan extension was linked to improved oxidative resistance, intestinal integrity, and autophagy.
  • Treatment reduced AKT and ERK activation, increased FOXO and GSK-3β activity, and modulated apoptosis.
  • No hyperglycemia was observed.

Conclusions:

  • GSK690693 demonstrates efficacy in extending lifespan and improving healthspan markers.
  • The compound modulates key aging-related signaling pathways.
  • GSK690693 represents a promising candidate for anti-aging therapies.
Keywords:
AKTAnti-agingAutophagyDrosophilaGSK690693

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