Increased MFG-E8 at neuromuscular junctions is an exacerbating factor for sarcopenia-associated denervation

Area of Science:

• Gerontology
• Muscle Biology
• Molecular Medicine

Background:

• Sarcopenia, an age-related muscle-wasting condition, has complex causes.
• Humoral factors, beyond muscle fibers, may play a role in sarcopenia's development.

Purpose of the Study:

• To identify humoral factors implicated in sarcopenia.
• To investigate the role of milk fat globule epidermal growth factor 8 (MFG-E8) in age-related muscle degeneration.

Main Methods:

• Utilized cytokine antibody arrays to screen for humoral factors in aged mice.
• Examined MFG-E8 protein levels in skeletal muscle, arterial walls, and neuromuscular junctions (NMJs).
• Assessed the impact of MFG-E8 deficiency on age-related denervation and muscle weakness.

Main Results:

• A significant increase in MFG-E8 was observed in the skeletal muscle of aged mice compared to young mice.
• Elevated MFG-E8 levels were found at arterial walls and NMJs in aged mice and humans.
• Increased MFG-E8 at NMJs preceded denervation and was more pronounced in fast-twitch muscles.

Conclusions:

• Increased MFG-E8 at NMJs is a key factor in age-related NMJ degeneration and sarcopenia.
• Genetic deficiency of MFG-E8 mitigated age-related muscle weakness and denervation.
• Targeting MFG-E8 presents a potential therapeutic avenue for sarcopenia prevention.