Age‐dependent capacity to accelerate protein synthesis dictates the extent of compensatory growth in skeletal muscle following undernutrition

Abstract

In both humans and animals, impaired growth during early life compromises adult lean body mass and muscle strength despite skeletal muscle's large regenerative capacity. To identify the significance of developmental age on skeletal muscle's capacity for catch‐up growth following an episode of undernutrition, mice were suckled on control dams fed a 20% protein diet or from birth to 11 (early malnutrition, EM) or 11 to 22 (late malnutrition, LM) days of age on dams fed a low‐protein (8%) diet. They were refed by cross‐fostering (EM) to control dams or weaning (LM) to a control (20% protein) diet. Hindlimb muscle mass and fractional protein synthesis rates (FSR) were measured on days 0, 2, 7 and 21 of refeeding (n=7–9 per age per treatment). On day 0, EM and LM muscles weighed 76% and 84% of age‐matched control values, respectively (P<0.001). After 21 d of refeeding, muscles weighed 94% (EM; NS) and 88% (LM; P<0.001) of control values. FSR were significantly higher in EM than control muscles 2 and 7 d after refeeding (P<0.01), whereas in LM pups, values were similar to controls at all ages. The increase in FSR in EM pups upon refeeding was attributable to increased ribosomal abundance. The data suggest that skeletal muscle's ability to effect catch‐up growth is dictated by a developmental stage‐dependent capacity for ribosome biogenesis. Funded by NIH AR46308 and USDA/ARS/CSREES 6250‐51000‐033