Aging exacerbates muscle loss induced by semaglutide treatment in female mice

In aged C57BL/6J mice, semaglutide causes dose-dependent skeletal muscle mass loss in females, including a 14.2% quadriceps reduction at 30 nmol/kg.

• Why it matters: GLP-1 receptor agonists can reduce lean mass, but prior work in young mice may not reflect older individuals at sarcopenia risk, and human gold-standard data are lacking.
• What they did: Male and female mice were made obese on a high-fat diet, then at 21 months received daily subcutaneous semaglutide (3 or 30 nmol/kg) or vehicle for 3 weeks; body composition used weekly NMR and muscle outcomes used organ mass and ex vivo electrical stimulation.
• The result: Muscle force-generating capacity was not compromised in semaglutide-treated females, while males showed a 19.2% reduction in extensor digitorum longus force at 30 nmol/kg, implying age- and sex-specific effects.

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