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Methionine restriction (MR) reduces inflammation and increases longevity. We studied the effects of MR (0.17% kCal methionine, 10% kCal fat) and MR + high-fat diet (HFD) (0.17% methionine, 45% kCal fat) and overload-induced hypertrophy on inflammation, angiogenesis and mitochondrial activity in the hind-limb muscle in 10- and 26-month-old male C57BL/6J mice. Plasma IL-6 concentrations were higher in old compared to young mice. M. plantaris hypertrophy was accompanied by increased p-Akt, without a significant change in Akt and VEGF levels. In young mice on a HFD or MR + HFD diet the SDH activity was higher than in those from mice on other diets, irrespective of overload. There were no significant differences in total NAD concentration in the m. gastrocnemius . MR enhanced the skeletal muscle hypertrophic response in old age that was accompanied with an increase in p-Akt without significant changes in muscle oxidative capacity, low-grade systemic inflammation, NAD, VEGF or Akt levels.

Methionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO 2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.