title: AMPK agonist AICAR delays the initial decline in lifetime-apex V̇o2 peak, while voluntary wheel running fails to delay its initial decline in female rats.
abstract: There has never been an outcome measure for human health more important than peak oxygen consumption (V̇o2 peak), yet little is known regarding the molecular triggers for its lifetime decline with aging. We examined the ability of physical activity or 5 wk of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration to delay the initial aging-induced decline in lifetime-apex V̇o2 peak and potential underlying molecular mechanisms. Experiment 1 consisted of female rats with (RUN) and without (NO RUN) running wheels, while experiment 2 consisted of female nonrunning rats getting the AMPK agonist AICAR (0.5 mg/g/day) subcutaneously for 5 wk beginning at 17 wk of age. All rats underwent frequent, weekly or biweekly V̇o2 peak tests beginning at 10 wk of age. In experiment 1, lifetime-apex V̇o2 peak occurred at 19 wk of age in both RUN and NO RUN and decreased thereafter. V̇o2 peak measured across experiment 1 was ∼25% higher in RUN than in NO RUN. In experiment 2, AICAR delayed the chronological age observed in experiment 1 by 1 wk, from 19 wk to 20 wk of age. RUN and NO RUN showed different skeletal muscle transcriptomic profiles both pre- and postapex. Additionally, growth and development pathways are differentially regulated between RUN and NO RUN. Angiomotin mRNA was downregulated postapex in RUN and NO RUN. Furthermore, strong significant correlations to V̇o2 peak and trends for decreased protein concentration supports angiomotin's potential importance in our model. Contrary to our primary hypothesis, wheel running was not sufficient to delay the chronological age of lifetime-apex V̇o2 peak decline, whereas AICAR delayed it 1 wk.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Toedebusch
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Ruegsegger
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: Joshua F
authors.initials: JF
authors.lastname: Braselton
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Heese
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: John C
authors.initials: JC
authors.lastname: Hofheins
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: Tom E
authors.initials: TE
authors.lastname: Childs
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas; and.
authors.forename: John P
authors.initials: JP
authors.lastname: Thyfault
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri boothf@missouri.edu.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Booth
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000737:chemistry*; D000375:Aging; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism; D000091082:Angiomotins; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005080:Exercise Test; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012265:Ribonucleotides / Q000378:metabolism*; D012420:Running; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: C545254:Amot protein, rat; D000091082:Angiomotins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D002950:Citrate (si)-Synthase; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide
keywords: RNA-seq; V̇o2 peak; cardiorespiratory fitness; physical activity; skeletal muscle; transcriptomics