The biological mechanisms responsible for the decline in skeletal muscle mass during aging remain unknown. It is hypothesized that elevations in the level of the acute phase C-reactive protein (CRP) negatively affect skeletal muscle mass in elderly. We examined the relationship between serum CRP and muscle mass in a population of active elderly women (65-70 years; n =23). Though all subjects were physically active, serum CRP levels were negatively associated to the amount of time spent in moderate-to-vigorous physical activity (R(2) = 0.20, P = 0.032) and to skeletal muscle mass (R(2) = 0.28, P = 0.009). We further aimed to determine the potential mechanisms behind the action of systemic inflammation on skeletal muscle by exposing myoblasts isolated from vastus lateralis to the different sera from each elderly woman. The doubling time (DT) of myoblasts increased when cells were exposed to sera with high CRP levels (R(2) = 0.27, P = 0.011), indicating that CRP contributes to the impairment of the proliferative rate of myoblasts in elderly. In order to further confirm our findings, we incubated human myoblasts in exogenous CRP. Exposition to exogenous CRP induced an increase in myoblast DT by 1.21-fold (P = 0.007) and a reduction in the expression of the proliferation marker ki-67 confirming the negative influence of CRP on myoblast proliferative rate. Collectively, these findings highlight the contribution of the systemic inflammatory status in the age-related decline in skeletal muscle function.