Sodium nitrite supplementation improves motor function and skeletal muscle inflammatory profile in old male mice.
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.
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and Jamie.Justice@colorado.edu.
Jamie N
JN
Justice
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Rachel A
RA
Gioscia-Ryan
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Lawrence C
LC
Johnson
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Micah L
ML
Battson
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Natalie E
NE
de Picciotto
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Hannah J
HJ
Beck
Texas Therapeutic Institute, Institute for Molecular Medicine, University of Texas Houston Health Sciences Center, Houston, Texas.
Hong
H
Jiang
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Amy L
AL
Sindler
Texas Therapeutic Institute, Institute for Molecular Medicine, University of Texas Houston Health Sciences Center, Houston, Texas.
Nathan S
NS
Bryan
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Roger M
RM
Enoka
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado; and.
Douglas R
DR
Seals
D000375:Aging / Q000187:drug effects*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D004353:Drug Evaluation, Preclinical; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012977:Sodium Nitrite / Q000494:pharmacology* / Q000627:therapeutic use
D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D012977:Sodium Nitrite
frailty; inflammation; mouse; nitric oxide; nitrite; physical function