Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice

Aging-related sarcopenia and osteoporosis are musculoskeletal disorders characterized by accelerated muscle and bone loss. Plasminogen activator inhibitor-1 (PAI-1), a fibrinolysis inhibitor, is involved in various pathological conditions, including sarcopenia and osteoporosis; however, its roles in aging-related sarcopenia and osteoporosis have yet to be fully investigated. Therefore, we investigated the roles of PAI-1 in aging-related sarcopenia and osteoporosis using PAI-1-gene-deficient and wild-type mice. Aging-related changes in muscle and bone were assessed by comparing the values in 24-month-old mice to those in 6-month-old mice. Regardless of sex, differences in muscle and bone parameters were observed between 24-month-old and 6-month-old mice. Aging increased PAI-1 expression in the gastrocnemius and soleus muscles of both female and male mice. PAI-1 deficiency significantly blunted aging-related decreases in lower limb muscle mass, muscle tissue weights, and grip strength in female mice but not in males. Moreover, PAI-1 deficiency significantly blunted aging-related cortical bone loss at the femurs and tibias of female but not male mice. These results indicate that PAI-1 is partly involved in aging-related sarcopenia and osteopenia in female mice, although the corresponding mechanisms remain unknown.