Abstract
The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1β, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.