Testosterone does not affect agrin cleavage in mobility-limited older men despite improvement in physical function.

Area of Science:

• Gerontology
• Endocrinology
• Neuromuscular Science

Background:

• Sarcopenia and physical dysfunction in some men are linked to neuromuscular junction (NMJ) destabilization, indicated by elevated C-terminal agrin fragment (CAF) serum levels.
• Testosterone administration shows potential for improving physical function, but its impact on serum CAF concentrations is not well understood.

Purpose of the Study:

• To evaluate the effect of testosterone administration on serum CAF levels in older, mobility-limited men with low testosterone.
• To assess the association between changes in CAF levels and improvements in muscle strength and physical function.

Main Methods:

• Analysis of serum CAF levels in participants of the Testosterone in Older Men with Mobility Limitations (TOM) Trial.
• Comparison of CAF level changes between testosterone and placebo groups.
• Evaluation of associations between CAF levels, testosterone levels (total and free), muscle strength, and physical function (loaded stair-climbing power).

Main Results:

• Testosterone administration significantly improved muscle strength and physical function.
• No significant reduction in serum CAF levels was observed with testosterone treatment.
• Changes in CAF levels showed no association with changes in total or free testosterone, muscle strength, or physical function.

Conclusions:

• Testosterone treatment in older men with mobility limitations and low testosterone does not decrease serum CAF levels.
• Improvements in physical function with testosterone are not linked to changes in CAF levels.
• The mechanisms underlying testosterone's benefits on physical function in this population likely involve pathways other than NMJ stabilization.