Aged (22-mo) female mice (n=35), obtained from the US NIH National Institute on Aging (NIA) Aged Rodent Colony, were randomly assigned to one of four groups: saline-treated sedentary ( n=9), nicotinamide N-methyltransferase inhibitor (NNMTi)-treated sedentary (10 mg/kg body weight; n=9), saline-treated progressive weighted wheel running (PoWeR; saline; n=10), and NNMTi-treated PoWeR (10 mg/kg body weight; n=7) . Group-housed Sed cohorts were compared to singly-housed PoWeR cohorts that underwent a 1-week introduction to an unweighted wheel, followed by eight weeks of weighted wheel running. Forelimb grip strength was assessed by a single NNMTi treatment-blinded investigator during week six and averaged across 2-4 trials/mouse. At the end of week 8, when mice were ~24.5-months-old, the strength of the right limb plantarflexor muscle complex was measured using an in vivo isometric peak tetanic torque technique and a fatigue test. After the fatigue test, mice were euthanized, and tissues were weighed and collected. Of note, hindlimb muscles from the right limb (the limb that underwent in vivo isometric peak tetanic torque and fatigue testing) were processed for immunohistochemistry to avoid acute effects of muscle functional testing on the proteome and metabolome. Hindlimb muscles from the left limb that did not undergo torque and fatigue testing were flash-frozen for proteome and metabolome analyses.
[doi:10.25345/C5ZK55Z12]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: exercise ; gastrocnemius ; nicotinamide N-methyltransferase inhibitor ; 5A-1MQ ; RT001 ; MS2 ; MS3
Principal Investigators: (in alphabetical order) |
Stan Watowich, Ridgeline Therapeutics, United States |
Submitting User: | RidgelineTx |
Dimet-Wiley AL, Latham CM, Brightwell CR, Neelakantan H, Keeble AR, Thomas NT, Noehren H, Fry CS, Watowich SJ.
Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice.
Sci Rep. 2024 Jul 5;14(1):15554. Epub 2024 Jul 5.
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