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.
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.
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DOI：
10.1152/physiolgenomics.00078.2015
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发表时间：
2016-02
影响因子：
4.6
通讯作者：
Ryan G. Toedebusch;Gregory N Ruegsegger;Joshua F. Braselton;Alexander J. Heese;John C Hofheins;T. Childs;J. Thyfault;F. Booth
中科院分区：
文献类型：
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作者：
Ryan G. Toedebusch;Gregory N Ruegsegger;Joshua F. Braselton;Alexander J. Heese;John C Hofheins;T. Childs;J. Thyfault;F. Booth
对于人类健康来说，从来没有比峰值耗氧量（V̇o2 峰值）更重要的结果衡量标准，但对于导致其寿命随衰老而下降的分子触发因素却知之甚少。我们检查了体力活动或 5 周 5-氨基咪唑-4-甲酰胺-1-β-d-呋喃核苷 (AICAR) 给药延缓最初衰老引起的寿命顶点 V̇o2 峰值下降的能力以及潜在的潜在分子机制。实验 1 由带（RUN）和不带（NO RUN）跑轮的雌性大鼠组成，而实验 2 由不跑轮的雌性大鼠组成，从 17 周龄开始皮下注射 AMPK 激动剂 AICAR（0.5 mg/g/天），持续 5 周。所有大鼠从 10 周龄开始频繁、每周或每两周进行 V̇o2 峰值测试。在实验 1 中，无论是跑步还是不跑步，终生最高 V̇o2 峰值均出现在 19 周龄，此后逐渐下降。实验 1 中测得的 V̇o2 峰值在“运行”状态下比“无运行”状态下高约 25%。在实验 2 中，AICAR 将实验 1 中观察到的实际年龄延迟了 1 周，从 19 周推迟到 20 周。 RUN 和 NO RUN 在心尖前和尖后显示出不同的骨骼肌转录组谱。此外，“跑步”和“不跑步”之间的生长和发育途径受到不同的调节。在 RUN 和 NO RUN 中血管动蛋白 mRNA 在峰后下调。此外，与 V̇o2 峰值和蛋白质浓度下降趋势的强烈显着相关性支持血管动蛋白在我们的模型中的潜在重要性。与我们的主要假设相反，车轮运行不足以延迟终生最高 V̇o2 峰值下降的实际年龄，而 AICAR 则将其延迟了 1 周。
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.