Arroum Tasnim, Hish Gerald A, Burghardt Kyle J, McCully James D, Hüttemann Maik, Malek Moh H
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
Unit for Laboratory Animal Medicine (ULAM), University of Michigan, Ann Arbor, MI 48109, USA.
Biomolecules. 2024 Apr 18;14(4):493. doi: 10.3390/biom14040493.
Mitochondria are the 'powerhouses of cells' and progressive mitochondrial dysfunction is a hallmark of aging in skeletal muscle. Although different forms of exercise modality appear to be beneficial to attenuate aging-induced mitochondrial dysfunction, it presupposes that the individual has a requisite level of mobility. Moreover, non-exercise alternatives (i.e., nutraceuticals or pharmacological agents) to improve skeletal muscle bioenergetics require time to be effective in the target tissue and have another limitation in that they act systemically and not locally where needed. Mitochondrial transplantation represents a novel directed therapy designed to enhance energy production of tissues impacted by defective mitochondria. To date, no studies have used mitochondrial transplantation as an intervention to attenuate aging-induced skeletal muscle mitochondrial dysfunction. The purpose of this investigation, therefore, was to determine whether mitochondrial transplantation can enhance skeletal muscle bioenergetics in an aging rodent model. We hypothesized that mitochondrial transplantation would result in sustained skeletal muscle bioenergetics leading to improved functional capacity.
Fifteen female mice (24 months old) were randomized into two groups (placebo or mitochondrial transplantation). Isolated mitochondria from a donor mouse of the same sex and age were transplanted into the hindlimb muscles of recipient mice (quadriceps femoris, tibialis anterior, and gastrocnemius complex).
The results indicated significant increases (ranging between ~36% and ~65%) in basal cytochrome oxidase and citrate synthase activity as well as ATP levels in mice receiving mitochondrial transplantation relative to the placebo. Moreover, there were significant increases (approx. two-fold) in protein expression of mitochondrial markers in both glycolytic and oxidative muscles. These enhancements in the muscle translated to significant improvements in exercise tolerance.
This study provides initial evidence showing how mitochondrial transplantation can promote skeletal muscle bioenergetics in an aging rodent model.
线粒体是“细胞的动力源”，线粒体功能进行性衰退是骨骼肌衰老的一个标志。尽管不同形式的运动方式似乎有利于减轻衰老引起的线粒体功能障碍，但这是以个体具备必要的活动能力为前提的。此外，用于改善骨骼肌生物能量学的非运动替代方法（即营养保健品或药物制剂）需要时间才能在靶组织中发挥作用，并且存在另一个局限性，即它们是全身性起作用，而非在需要的局部起作用。线粒体移植是一种新型的定向治疗方法，旨在提高受线粒体缺陷影响的组织的能量产生。迄今为止，尚无研究将线粒体移植作为一种干预措施来减轻衰老引起的骨骼肌线粒体功能障碍。因此，本研究的目的是确定线粒体移植是否能增强衰老啮齿动物模型中的骨骼肌生物能量学。我们假设线粒体移植将导致骨骼肌生物能量学持续改善，从而提高功能能力。
将15只24月龄雌性小鼠随机分为两组（安慰剂组或线粒体移植组）。将从同性别、同年龄供体小鼠分离的线粒体移植到受体小鼠的后肢肌肉（股四头肌、胫骨前肌和腓肠肌复合体）中。
结果表明，与安慰剂组相比，接受线粒体移植的小鼠的基础细胞色素氧化酶和柠檬酸合酶活性以及ATP水平显著提高（约36%至约65%）。此外，糖酵解和氧化肌肉中线粒体标志物的蛋白表达均显著增加（约两倍）。这些肌肉中的改善转化为运动耐力的显著提高。
本研究提供了初步证据，表明线粒体移植如何在衰老啮齿动物模型中促进骨骼肌生物能量学。
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