VEGFA Promotes Skeletal Muscle Regeneration in Aging

Area of Science:

• Muscle regeneration and aging research
• Molecular mechanisms of skeletal muscle repair
• Vascular Endothelial Growth Factor (VEGF) signaling in aging

Background:

• Skeletal muscle regeneration capacity declines with age.
• Vascular Endothelial Growth Factor A (VEGF-A) levels are altered during aging.
• The specific role of VEGF-A in age-related muscle regeneration is not fully understood.

Purpose of the Study:

• To investigate the role of VEGF-A in age-related skeletal muscle regeneration.
• To determine if modulating VEGF-A levels can improve muscle repair in aging mice.

Main Methods:

• Cryoinjury model in the tibialis anterior muscle of young and old C57BL/6 mice.
• Assessment of regenerating myofiber cross-sectional area (CSA) and capillary density.
• Utilized young mice with reduced systemic VEGF-A activity (VEGF^lo) and ML228 (hypoxia signaling activator) to modulate VEGF-A levels.

Main Results:

• Older mice exhibited significantly smaller regenerating myofiber CSA compared to young mice, correlating with lower muscle VEGF-A protein levels.
• Young VEGF^lo mice showed a marked reduction in regenerating fiber CSA post-injury.
• ML228 treatment increased muscle VEGF-A levels and augmented regenerating fiber CSA in old and VEGF^lo mice, but not in young controls.

Conclusions:

• VEGF-A levels are diminished in aging muscle and contribute to impaired regeneration.
• Restoring VEGF-A levels, for example, through hypoxia signaling activation, can enhance muscle regeneration in aged and VEGF-deficient conditions.
• VEGF-A presents a potential therapeutic target for counteracting age-related skeletal muscle loss and improving regenerative capacity.