AMPK agonist AICAR delays the initial decline in lifetime-apex (V) over dotO(2) (peak), while voluntary wheel running fails to delay its initial decline in female rats

作者：Toedebusch Ryan G; Ruegsegger Gregory N; Braselton Joshua F; Heese Alexander J; Hofheins John C; Childs Tom E; Thyfault John P; Booth Frank W^*

来源：Physiological Genomics, 2016, 48(2): 101-115.

DOI：10.1152/physiolgenomics.00078.2015

• physical activity
• RNA-seq
• transcriptomics
• skeletal muscle
• cardiorespiratory fitness
• (V) over dotO(2) (peak)

There has never been an outcome measure for human health more important than peak oxygen consumption (V) over dotO(2) (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-beta-D-ribofuranoside (AICAR) administration to delay the initial aging-induced decline in lifetime-apex (V) over dotO(2) (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 (V) over dotO(2) (peak) tests beginning at 10 wk of age. In experiment 1, lifetime-apex (V) over dotO(2) (peak) occurred at 19 wk of age in both RUN and NO RUN and decreased thereafter. (V) over dotO(2) (peak) measured across experiment 1 was similar to 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 (V) over dotO(2) (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 (V) over dotO(2) (peak) decline, whereas AICAR delayed it 1 wk.

• 出版日期2016-2-1