Exposure to High Altitude Promotes Loss of Muscle Mass That Is Not Rescued by Metformin

Area of Science:

• Physiology
• Altitude Medicine
• Muscle Biology

Background:

• High altitude (HA) exposure is known to induce muscle atrophy.
• Metformin (Met), a drug used for diabetes, has been investigated for its potential to mitigate age- and obesity-related muscle loss.

Purpose of the Study:

• To investigate if metformin can attenuate muscle atrophy induced by high altitude exposure.
• To examine the effects of HA and Met on muscle mass, cellular size, body composition, and molecular atrophy mediators.

Main Methods:

• Male and female C57Bl6 mice were exposed to simulated HA (5,200m) for 4 weeks, with controls at resident altitude (2,180m).
• Metformin was administered daily (200 mg/kg/day) via drinking water.
• Muscle mass, myocyte size, body composition, and expression of atrophy-related genes were analyzed.

Main Results:

• HA exposure led to reduced body weight and hind limb complex (HLC) mass in mice.
• Metformin did not prevent HLC mass loss or reduce myocyte size.
• Atrophy markers were activated in a sex-dependent manner; myostatin was upregulated at HA, and Met further increased it in females.

Conclusions:

• High altitude exposure causes significant muscle mass loss, particularly in males.
• Metformin is ineffective in preventing or attenuating HA-induced muscle atrophy.
• Further research is needed to identify effective interventions for preserving muscle mass at high altitudes.