Study of Therapeutic Effects of Losartan for Sarcopenia Based on the F344xBN Rat Aging Model

Abstract

Background/Aim: Sarcopenia is an age-related disease in which muscle mass and strength are markedly reduced. There are few effective treatments, but the angiotensin II receptor antagonist losartan has been reported to be effective. Our aim was to evaluate the therapeutic effectiveness of losartan for sarcopenia and explore the underlying mechanisms. Materials and Methods: We investigated body weight, muscle mass (gastrocnemius, soleus, peroneus longus, and tibialis anterior muscles), and serum markers in an aged rat model population divided into four treatment groups: Control, exercise, losartan, and exercise plus losartan. The rats were sacrificed at 6, 12, or 18 months after the start of the experiment and autopsies were performed. Results: Compared with the control group, average muscle mass and weight increased in the two groups treated with losartan. AKT serine/threonine kinase (AKT) and extracellular signal-regulated kinase (ERK) muscle growth factors increased in the peroneus longus. mechanistic target of rapamycin kinase (mTOR) increased in tibialis anterior, peroneus longus, and soleus. Conclusion: Losartan treatment slowed muscle degeneration and activated the PI3K-AKT- mTOR and ERK/mitogen-activated protein kinase signalling pathways required for production of muscle growth factors when combined with exercise.