The muscle protein density associates with radiodensity, strength, damage, unloading and disease: evidence from humans & mice.

Abstract

Skeletal muscle remodeling affects muscle functionality, quality and mass. The protein density is an important determinant of muscle quality, that can be readily assessed, but which is rarely reported. This study assessed how muscle protein density responds to challenges such as exercise, injury, immobilization and disease, and associated this with measures of lean mass, radiodensity, functionality and damage. The protein density was determined in human muscle biopsies from older adults (65-83 years) and young males (18-35 years), and in murine muscles. The protein density was compared between challenged conditions (disease, injury, eccentric exercise, immobilization) and a control condition, and/or associated with i) measures of muscle volume and radiodensity (via computed tomography), ii) molecular measures of damage and iii) measures of strength. Protein density correlated with upper leg lean mass (r=0.4468; p=0.0371) and radiodensity (r=0.5085; p=0.0157) in older adults. Eccentric exercise decreased the protein density with 9% (p=0.0248) in young adults, which correlated with decreases in strength (r>0.79; p<0.01). In murine disease and injury models, muscle loss (-12%; -90%; p<0.01) was accompanied by a loss of protein density (-3; -21%), in a muscle- and time-dependent way. Interestingly, the immobilization-induced muscle loss (-16%; p=0.0069) was accompanied by a higher protein density (+8%; p=0.0293) compared to the non-immobilized leg. In conclusion, muscle protein density associates with muscle mass and muscle function. Muscle protein density can be a valuable biomarker that provides more insights into the mechanisms that underlie muscle adaptations due to disease, aging, injury and exercise.