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Ribosome abundance regulates the recovery of skeletal muscle protein mass upon recuperation from postnatal undernutrition in mice

Inadequate nutrient intake during early life can programme a low adult muscle mass. We have used a mouse model to identify the developmental window when the skeletal musculature is vulnerable to programming and to identify factors that limit the muscle's ability to respond when normal nutrition is restored. We established that the developmental age when nutritional rehabilitation occurs following an episode of poor nutrition, rather than the duration or severity of the nutrient restriction, is the critical factor that determines if muscle mass can be recuperated. The ability to recover depends on whether the muscles’ translational capacity, i.e. ribosomal abundance, can increase sufficiently to raise protein synthesis rates sufficiently to accelerate protein deposition. We show that the ability to increase ribosomal abundance was associated with increased expression of the nucleolar transcription factor UBF (upstream binding factor), which regulates RNA polymerase 1 activity and rRNA transcription, the limiting factor for ribosomal production.