Dataset Information

Aged Mouse Muscle: Sedentary or Exercised Animals with or without Nicotinamide N-methyltransferase Inhibitor Treatment

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Stan Watowich

PROVIDER: MSV000094700 | MassIVE | Tue May 07 04:49:00 BST 2024

SECONDARY ACCESSION(S): PXD052072

REPOSITORIES: MassIVE

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Publications

Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice.

Dimet-Wiley Andrea L AL Latham Christine M CM Brightwell Camille R CR Neelakantan Harshini H Keeble Alexander R AR Thomas Nicholas T NT Noehren Haley H Fry Christopher S CS Watowich Stanley J SJ

Scientific reports 20240705 1

Human hallmarks of sarcopenia include muscle weakness and a blunted response to exercise. Nicotinamide N-methyltransferase inhibitors (NNMTis) increase strength and promote the regenerative capacity of aged muscle, thus offering a promising treatment for sarcopenia. Since human hallmarks of sarcopenia are recapitulated in aged (24-month-old) mice, we treated mice from 22 to 24 months of age with NNMTi, intensive exercise, or a combination of both, and compared skeletal muscle adaptations, includ ...[more]

PMID: 38969654

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