Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice

Abstract

Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.

Keywords: aging; insulin resistance; muscle mass; myostatin; sarcopenia.

Fig. 1.

ATA 842 treatment increases body weight and muscle mass. Initial and final body weight (A), muscle mass (B), and body fat (C) of young mice fed RC. Initial and final body weight (D), muscle mass (E), and body fat (F) of young mice fed HFD. Initial and final body weight (G), muscle mass (H), and body fat (I) of old mice fed RC. Plasma lactate (J), hepatic triglycerides (K), and muscle triglycerides (L) of young mice fed RC or HFD and old mice fed RC. Data are represented as mean ± SEM (n = 10 per group).

Fig. 2.

ATA 842 treatment increases gastrocnemius weight and grip strength. Gastrocnemius weight of young mice fed RC or HFD and old mice fed RC (A). Initial and final grip strength of young mice fed RC (B) or HFD (C) and old mice (D) fed RC. Data are represented as mean ± SEM (n = 10 per group).

Fig. 3.

ATA 842 treatment does not increase insulin sensitivity in young mice. Time-course of plasma glucose (A) and GIR (B) during the hyperinsulinemic-euglycemic clamp. Whole-body glucose uptake (C) during the steady-state period (final 40 min) of the clamp, and basal (D) and clamped (E) EGP. Data are represented as mean ± SEM (n = 10 per group). *P < 0.01 compared with vehicle-treated mice.

Fig. 4.

ATA 842 treatment subtly improves insulin sensitivity in old mice. Time course of plasma glucose (A) and GIR (B) during the hyperinsulinemic-euglycemic clamp. Whole-body glucose uptake (C) during the steady-state period (final 40 min) of the clamp, and basal and clamped (D) EGP. Skeletal muscle and white adipose tissue 2-deoxyglucose uptake (E) during the clamp. Data are represented as mean ± SEM (n = 10 per group).