Ageing-related structural and cellular alterations in the mouse muscle-tendon junction

Area of Science:

• Biomedical Engineering
• Gerontology
• Musculoskeletal Biology

Background:

• The muscle-tendon junction (MTJ) is crucial for force transmission but is prone to injury, especially with age.
• Mechanisms of MTJ aging and functional decline are poorly understood.
• Age-related injuries impact mobility and quality of life in aging populations.

Purpose of the Study:

• To comprehensively characterize age-related structural and cellular changes at the mouse Achilles MTJ.
• To investigate the role of cellular senescence and vascularity in MTJ aging.
• To identify potential therapeutic targets for preserving MTJ function in older adults.

Main Methods:

• Utilized high-resolution micro-computed tomography (µCT) and confocal microscopy for 3D structural analysis.
• Employed in situ hybridization and immunofluorescence to assess senescence markers (p16, p21) in specific cell types.
• Compared young (3-month-old) and old (23-month-old) male mice.

Main Results:

• Reduced muscle fiber diameter (27%) and pennation angle (19%) in old mice, suggesting decreased force generation.
• Significant reduction in endothelial cell volume (49%), indicating loss of vascularity.
• Marked increase in senescence markers p16 and p21 in MTJ-specific cells (270% and 310% respectively) and endothelial cells with age.

Conclusions:

• Aging significantly alters MTJ structure and cellular composition, characterized by reduced vascularity and increased cellular senescence.
• MTJ-specific cells and vascular endothelial cells are particularly susceptible to aging.
• These age-related cellular changes likely contribute to MTJ functional decline and injury susceptibility.