Mitochondrial energetics is impaired in vivo in aged skeletal muscle.

Mitochondrial energetics is impaired in vivo in aged skeletal muscle.
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DOI:
10.1111/acel.12147
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发表时间:
2014-02
期刊:
影响因子:
7.8
通讯作者:
Diolez P
Diolez P
中科院分区:
生物学1区
文献类型:
--
作者:
Gouspillou G;Bourdel-Marchasson I;Rouland R;Calmettes G;Biran M;Deschodt-Arsac V;Miraux S;Thiaudiere E;Pasdois P;Detaille D;Franconi JM;Babot M;Trézéguet V;Arsac L;Diolez P

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随着年龄的增长,大多数骨骼肌会逐渐失去质量和力量,这一过程被称为石棺减少症。线粒体能量学中与衰老相关的缺陷被认为与骨质疏松症有关。然而,肌肉线粒体氧化磷酸化随年龄的变化仍然是一个极具争议性的问题,迫切需要综合的方法来确定线粒体生物能量学在衰老的骨骼肌中是否受损。为解决这一问题,首次采用模块化对照分析方法和31P核磁共振波谱测量能量代谢产物相结合的方法,在成年(6月龄)和老年(21月龄)雄性Wistar大鼠的腓肠肌中首次研究了线粒体生物能量学。使用这种创新的方法,我们发现在老年骨骼肌中,线粒体氧化磷酸化对收缩诱导的ATP需求增加的体内反应性(弹性)显著降低,这种降低在低收缩活动下尤其明显。与体内线粒体能量学中与衰老相关的缺陷相一致,我们发现从衰老骨骼肌分离的线粒体对ADP的亲和力显著降低。总之,这项研究的结果表明,线粒体生物能量学在衰老的骨骼肌中可以在体内有效地改变,并为这种现象提供了一个新的细胞学基础。
With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with 31P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness (‘elasticity’) of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.
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