Effects of Age on Na(+),K(+)-ATPase Expression in Human and Rodent Skeletal Muscle

Abstract

The maintenance of transmembrane Na(+) and K(+) concentration gradients and membrane potential is vital for the production of force in skeletal muscle. In aging an inability to maintain ion regulation and membrane potential would have adverse consequences on the capacity for performing repeated muscle contractions, which are critical for everyday activities and functional independence. This short review focusses on the effects of aging on one major and vital component affecting muscle Na(+) and K(+) concentrations, membrane potential and excitability in skeletal muscle, the Na(+),K(+)-ATPase (Na(+),K(+)-pump, NKA) protein. The review examines the effects of age on NKA in both human and rodent models and highlights a distant lack of research in NKA with aging. In rodents, the muscle NKA measured by [(3)H]ouabain binding site content, declines with advanced age from peak values in early life. In human skeletal muscle, however, there appears to be no age effect on [(3)H]ouabain binding site content in physically active older adults between 55 and 76 years compared to those aged between 18 and 30 years of age. Analysis of the NKA isoforms reveal differential changes with age in fiber-types in both rat and humans. The data show considerable disparities, suggesting different regulation of NKA isoforms between rodents and humans. Finally we review the importance of physical activity on NKA content in older humans. Findings suggest that physical activity levels of an individual may have a greater effect on regulating the NKA content in skeletal muscle rather than aging per se, at least up until 80 years of age.

Keywords: Na+K+-pump; [3H]ouabain; age; single fiber.

Figure 1

Human skeletal muscle [³H]ouabain binding with aging and physical activity from studies conducted in the Clausen laboratory (Aarhus, Denmark). Data from early papers investigating [³H]ouabain binding in older adults from different studies measured in the same laboratory to ensure comparisons are made utilizing the same methodology. 1. Indicates data from (Klitgaard and Clausen, 1989), 2. from (Dørup et al., 1988a), and 3. from (Dørup et al., 1988b). Data from 2 to 3 were from healthy control subjects in studies undertaking comparison against clinical populations. These clinical population data have not been included in this figure. *Different to 68 years (no exercise), ⁺ different to young (active), p < 0.05.

Figure 2

Muscle [³H]ouabain binding does not change with age in human skeletal muscle. Muscle [³H]ouabain binding site content collated from data collected on healthy young and healthy older adults from the McKenna research group between 2012 and 2016. (A) Shows the data combined into two discrete age groups and analyzed by unpaired t-test (p = 0.53). (B) Shows all data plotted into relevant decades of life analyzed by one-way ANOVA (p = 0.30); the mean of each group is also shown as a horizontal line.