Aging is associated with motor declines that lead to functional limitations and disability, necessitating the development of
therapies to slow or reverse these events. We tested the hypothesis that
sodium nitrite supplementation attenuates declines in motor function in older C57BL/6 mice. Motor function was assessed using a battery of tests (grip strength, open-field distance, rota-rod endurance) in old animals (age 20-24 mo) at baseline and after 8 wk of
sodium nitrite (old
nitrite, n = 22, 50 mg/liter) or no treatment (old control, n = 40), and in young reference animals (3 mo, n = 87). Eight weeks of
sodium nitrite supplementation improved grip strength (old
nitrite, +12.0 ± 14.9% vs. old control, +1.5 ± 15.2%, P < 0.05) and open field distance (old
nitrite, +9.5 ± 7.7%, P < 0.01 vs. old control, -28.1 ± 2.0%) and completely restored rota-rod endurance-run time (old
nitrite, +3.2 ± 7.1%, P < 0.01 vs. old control, -21.5 ± 7.2%; old
nitrite after treatment P > 0.05 vs. young reference). Inflammatory
cytokines were markedly increased in quadriceps of old compared with young reference animals (by ELISA,
interleukin-1β [IL-1β] 3.86 ± 2.34 vs. 1.11 ± 0.74, P < 0.05;
interferon-gamma [INF-γ] 8.31 ± 1.59 vs. 3.99 ± 2.59, P < 0.01;
tumor necrosis factor-alpha [TNF-α] 1.69 ± 0.44 vs. 0.76 ± 0.30 pg/ml, P < 0.01), but were reduced to young reference levels
after treatment (old
nitrite, IL-1β 0.67 ± 0.95; INF-γ 5.22 ± 2.01, TNF-α 1.21 ± 0.39 pg/ml, P < 0.05 vs. old control, P > 0.05 vs. young reference).
Cytokine expression and treatment (old
nitrite vs. old control) predicted strength (R(2) = 0.822, P < 0.001, IL-1β, INF-γ, group), open field distance (R(2) = 0.574, P < 0.01, IL-1β, group) and endurance run time (R(2) = 0.477, P < 0.05, INF-γ). Our results suggest that
sodium nitrite improves motor function in old mice, in part by reducing low-grade
inflammation in muscle.