Background. Nuclear factor kappa B (NF-kappa B) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and mix. Methods. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappa B signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the 13 subunit of IkB kinase (IKK beta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKB alpha), and nuclear content of NF-kappa B subunits p50 and p65. Results. When compared with YS. OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBa than OA and 61% more pIKBa than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of Conclusions. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBa. A sedentary lifestyle appears to play some role in increased IKB alpha however, further research is needed to identify downstream effects of this increase.