Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men

Abstract

Background: Nuclear factor kappa B (NF-kappaB) 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 age.

Methods: The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB 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 beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB 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 pIKBalpha than OA and 61% more pIKBalpha 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 IKKbeta.

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 pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

Figure 1.

Aging in the absence of physical activity leads to significant decreases in lower limb lean mass. (A) Whole-body lean mass (g/cm²) in young, physically inactive (gray), older, physically inactive (red), and older, physically active (blue) individuals. (B) Lower limb lean mass (g/cm²) of the nondominant leg. Bars depict means; error bars indicate standard error. Groups sharing a common symbol significantly different at *p < .05.

Figure 2.

Muscle force production declines significantly as an effect of age and/or inactivity. (A) Maximal isokinetic peak torque (Nm) production of the quadriceps extensors of the nondominant limb in young, physically inactive (gray), older, physically inactive (red), and older, physically active (blue) individuals. (B) Maximal isokinetic peak torque relative to body mass (Nm/kg) of the quadriceps extensors of the nondominant limb. (C) Maximal isokinetic power (W) production of the quadriceps extensors of the nondominant limb. Bars depict means; error bars indicate standard error. Groups sharing a common symbol significantly different at p < .05 * p < .05 between YS/OS. † p < .05 between OA/OS.

Figure 3.

Nuclear factor kappa B (NF-κB) activity is elevated by advanced age, and p65 is the critical subunit for regulating NF-κB signaling in age-related muscle atrophy. Skeletal muscle messenger RNA (mRNA) expression of IKKβ (IKKβ/β-actin) from biopsies taken from the vastus lateralis of the dominant limb in (A) young, physically inactive (gray), older, physically inactive (red), and older, physically active (blue) individuals. (B) Skeletal muscle content of IKBα phosphorylated at serine 32 (U/mg protein) from vastus lateralis biopsies. (C) Nuclear p50 (OD₄₅₀/mg protein) from skeletal muscle biopsies of the vastus lateralis. (D) Nuclear p65 (OD₄₅₀/mg protein) from skeletal muscle biopsies of the vastus lateralis. Bars depict means; error bars indicate standard error. Groups sharing a common symbol significantly different at p  <  .05 * p < .05 between YS/OS. † p < .05 between OA/OS.