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Fasting improves metabolic health, but is also associated with loss of lean body mass. We investigated if old mice are less resistant to fasting-induce muscle wasting than adult mice. We compared changes in skeletal muscles and fat distribution in C57BL/6J mice subjected to 48-hour fasting at adult (6-month old) or old (24-month old) age. Old mice lost less weight (11.9 ± 1.5 vs 16.9 ± 2.8%, p < 0.001) and showed less (p < 0.01) pronounced muscle wasting than adult mice. Extensor digitorum longus (EDL) muscle force decreased only in adult mice after fasting. Serum IGF-1 levels were higher (p < 0.01) and showed greater (p < 0.01) decline in adult mice compared to old mice. Phosphorylation of 4EBP1 was reduced in the gastrocnemius muscles of adult mice only. Energy expenditure was slower in old mice and showed smaller fasting-induced decline than in adult mice when adjusted for variations in physical activity. There was a loss of fat mass in both age groups, but it was more pronounced in adult mice than old mice. Our results suggest that ageing-related decrease in metabolic rate protects old mice from skeletal muscle wasting during fasting. • We investigated effects of fasting on body composition of adult and old C57BL/6J mice. • 48-hour fasting was associated with low physical activity and greater decrease serum IGF-1 in adult compared to old mice. • Fasting induced significant muscle wasting and force loss only in adult mice. • Reduced metabolic rate protects old mice from excessive muscle wasting during fasting. [ABSTRACT FROM AUTHOR]

Myostatin is an inhibitor of skeletal muscle growth and might be involved in adaptations to caloric restriction (CR). We compared responses to 12-week 30% CR in male mice of Berlin high strain with myostatin dysfunction (BEH) and wild-type myostatin (BEH+/+). BEH mice were heavier than BEH+/+ mice (58.8 ± 2.0 versus 53.1 ± 2.7 g, p < 0.001), had 1.8-fold greater hind limb muscle mass and were less (p < 0.05) physically active when fed ad libitum. After CR, BEH and BEH+/+ strains experienced similar weight loss (24.7 ± 5.7 versus 20.6 ± 6.5%, p > 0.05, respectively) and decreases (p < 0.001) in plasma IGF-1 and total cholesterol, but loss of hind limb muscle mass was greater (p < 0.001) in BEH mice than BEH+/+ mice. BEH mice had better (p < 0.001) glucose tolerance and showed smaller (p < 0.05) improvements of it than BEH+/+ mice after CR (1038.2 ± 174.7 versus 744.4 ± 95.8 glucose mM× 120 min, p < 0.01 for BEH; 1365.8 ± 218.5 versus 831.5 ± 134.4 glucose mM ×120 min, p < 0.001, for BEH+/+, respectively). In summary, myostatin dysfunction is associated with muscle hypertrophy and high glucose tolerance, but greater muscle wasting and smaller improvements in glucose tolerance in response to CR. • We investigated effects of myostatin dysfunction and caloric restriction in Berlin high mouse strain. • 12 weeks of 30% caloric restriction induced loss of fat and muscle mass, lowered plasma triacylglycerol and cholesterol. • Myostatin dysfunction was associated with greater loss of hind limb muscle mass and attenuated improvements in glucose tolerance of mice • Myostatin dysfunction does not protect from muscle wasting during caloric restrriction. [ABSTRACT FROM AUTHOR]