Sodium nitrite supplementation improves motor function and skeletal muscle inflammatory profile in old mice (LB817)

Aging is associated with motor impairments that reduce quality of life and represent a major healthcare burden, necessitating the development of potential therapies to slow or reverse age‐related functional declines. Chronic low‐grade inflammation develops with advancing age and may be a primary mediator of functional declines. We tested the hypothesis that sodium nitrite (SN) supplementation reverses age‐related motor dysfunction and reduces muscle inflammation. Motor function was assessed using a battery of tests (grip strength [GS], open field distance [OFD] and rota‐rod endurance run [ER]) in young (Y, 3 mo, n=87), old (O, 24 mo, n=40) and old mice treated with SN (ON, n=22, 50 mg/L in drinking water, 8 wk). Function was impaired in O vs. Y (GS: 97.0 ± 18.6 vs. 130 ± 14 g; OFD: 1183 ± 453 vs. 1859 ± 265 cm; ER: 8.4 ± 6.4 vs. 14.4 ± 5.9 min; all p<0.05) and improved with SN (GS: 111 ± 17.0 g; OFD: 1486 ± 485 cm; ER: 14.9 ± 5.1 min, all p<0.05 vs. O). Inflammatory cytokine levels were markedly increased in skeletal muscle of O vs. Y (ELISA: interleukin‐1 β [IL‐1β]: 3.86 ± 2.34 vs. 1.11 ± 0.74; interferon gamma [INFγ]: 8.31 ± 1.59 vs. 3.99 ± 2.59; tumor necrosis factor alpha [TNFα]: 1.69 ± 0.44 vs. 0.76 ± 0.30 pg/mL, all p<0.05), but returned to levels not different than Y with SN (ON: IL‐1β: 0.67 ± 0.95, INFγ: 5.22 ± 2.01, TNFα: 1.21 ± 0.39 pg/mL, all p0.05 vs. Y). Regression models demonstrated that cytokine expression and treatment group (O vs. ON) predicted GS (R 2 = 0.822, p<0.001, IL‐1β, INFγ, group), OFD (R 2 = 0.574, p<0.01, IL‐1β, group) and ER (R 2 = 0.477, p<0.05, INFγ). Our results suggest that SN initiated late in life preserves motor function in old mice, possibly by reducing inflammation in skeletal muscle. Grant Funding Source : Supported by NIH AG013038 and AG000279