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

Skeletal muscle remodeling affects muscle functionality, quality, and mass. The protein density is an important determinant of muscle quality, which can be readily assessed but 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 yr) and young males (18-35 yr), and in murine muscles. The protein density was compared between challenged conditions (disease, injury, eccentric exercise, and immobilization) and a control condition, and/or associated with <i>1</i>) measures of muscle volume and radiodensity (via computed tomography), <i>2</i>) molecular measures of damage, and <i>3</i>) measures of strength. Protein density correlated with upper leg lean mass (<i>r</i> = 0.4468; <i>P</i> = 0.0371) and radiodensity (<i>r</i> = 0.5085; <i>P</i> = 0.0157) in older adults. Eccentric exercise decreased the protein density with 9% (<i>P</i> = 0.0248) in young adults, which correlated with decreases in strength (<i>r</i> > 0.79; <i>P</i> < 0.01). In murine disease and injury models, muscle loss (-12%; -90%; <i>P</i> < 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%; <i>P</i> = 0.0069) was accompanied by a higher protein density (+8%; <i>P</i> = 0.0293) compared with the nonimmobilized 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.<b>NEW & NOTEWORTHY</b> Skeletal muscle tissue is highly plastic and its remodeling takes place at the level of functionality, muscle mass, and quality, but this latter remains often understudied. Muscle protein density is one determinant of muscle quality that can be readily assessed. The muscle protein density is responsive to various challenges such as injury, disease, and immobilization, and is associated with muscle mass, functionality, and radiodensity. Muscle protein density provides valuable insights into the mechanisms underlying muscle adaptation.