Age-related loss of skeletal muscle mass (sarcopenia) adversely affects muscle tissue-specific and whole-body homeostasis, suggesting an undefined relationship between muscle mass and whole-body circulation that underlies the etiology of sarcopenia. To investigate, 344 metabolites and analytes were measured in serum from 19 older adults. Arginine and proline metabolism was the pathway most closely associated with skeletal muscle index (SMI), a measure of skeletal muscle mass. Subsequently, gene expression of related transport and regulatory enzymes was measured.

Younger and older adult muscle tissue had similar inflammatory signaling and gene expression of CAT-1 and CAT-2, the cationic amino acid transporters that allow arginine into muscle. However, the proinflammatory cytokine TNF-α increased CAT-2 gene expression in differentiated human primary skeletal muscle cells. TNF-α also altered the expression of arginine metabolic genes regulating polyamine synthesis and proline production. Changes in arginine availability and metabolism may underlie the relationship between inflammation and skeletal muscle mass.