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Related Experiment Video

Updated: Oct 14, 2025

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
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Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways.

Ruzhou Zhao1, Xingcheng Zhao1, Xiaobo Wang1

  • 1Department of Aerospace Physiology, Air Force Medical University, Xi'an, China.

Cell Death & Disease
|November 4, 2021
PubMed
Summary

Fasting for 72 hours improves survival in extreme hypoxia by reducing tissue injury and maintaining cardiac function. This fasting preconditioning strategy enhances rapid hypoxic adaptation by suppressing mTOR activity.

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Area of Science:

  • Physiology
  • Cellular Biology
  • Environmental Medicine

Background:

  • Rapid adaptation to hypoxic environments remains a significant challenge with no established strategies.
  • Understanding the mechanisms underlying hypoxic tolerance is crucial for various medical and survival applications.

Purpose of the Study:

  • To investigate the efficacy of fasting preconditioning as a strategy for rapid adaptation to extreme hypoxia.
  • To elucidate the molecular mechanisms, particularly the role of mTOR signaling, in fasting-mediated hypoxic tolerance.

Main Methods:

  • Rats underwent a 72-hour fasting preconditioning period.
  • Physiological parameters including tissue injury, cardiac function, and survival rates were assessed under extreme hypoxia.
  • Molecular analyses focused on blood glucose levels, mTOR activity, protein synthesis, lipogenesis, mitochondrial oxygen utilization, reactive oxygen species (ROS) generation, and mitophagy.

Main Results:

  • Fasting preconditioning significantly improved survival rates in rats exposed to extreme hypoxia.
  • Fasting reduced tissue injuries and preserved cardiac function.
  • Mechanistically, fasting suppressed tissue mTOR activity by reducing blood glucose, which decreased ATP consumption and enhanced mitochondrial oxygen utilization via reduced ROS generation and increased mitophagy.

Conclusions:

  • Fasting preconditioning is a viable strategy for achieving rapid adaptation to extreme hypoxic conditions.
  • The mechanistic pathway involves mTOR inhibition, leading to improved energy balance and mitochondrial function under hypoxia.
  • Targeting mTOR signaling presents a novel therapeutic strategy for enhancing acute hypoxic tolerance.