Laboratory of Molecular Biology of Exercise, University of Campinas, Limeira, Brazil.
Department of Physical Education, Institute of Biosciences, São Paulo State University, Rio Claro, Brazil.
J Gerontol A Biol Sci Med Sci. 2020 Nov 13;75(12):2258-2261. doi: 10.1093/gerona/glaa059.
The impairment of the mitochondrial functions is a hallmark of aging. During aging, there is a downregulation of two mechanisms strictly associated with mitochondrial integrity, including the mitonuclear imbalance (eg, imbalance in mitochondrial- versus nuclear-encoded mitochondrial proteins) and the mitochondrial unfolded protein response (UPRmt). Here, we evaluated the effects of aerobic exercise in the mitonuclear imbalance and UPRmt markers in the skeletal muscle of old mice. We combined the physiological tests, molecular and bioinformatic analyzes to evaluate the effects of 4 weeks of aerobic exercise training on mitonuclear imbalance and UPRmt markers in the skeletal muscle of young (2 months) and aged (24 months) C57BL/6J mice. Initially, we found that aging reduced several mitochondrial genes in the gastrocnemius muscle, and it was accompanied by the low levels of UPRmt markers, including Yme1l1 and Clpp mRNA. As expected, physical training improved the whole-body metabolism and physical performance of aged mice. The aerobic exercise increased key proteins involved in the mitochondrial biogenesis/functions (VDAC and SIRT1) along with mitochondrial-encoded genes (mtNd1, mtCytB, and mtD-Loop) in the skeletal muscle of old mice. Interestingly, aerobic exercise induced the mitonuclear imbalance, increasing MTCO1/ATP5a ratio and UPRmt markers in the skeletal muscle, including HSP60, Lonp1, and Yme1L1 protein levels in the gastrocnemius muscle of aged mice. These data demonstrate that aerobic exercise training induced mitonuclear imbalance and UPRmt in the skeletal muscle during aging. These phenomena could be involved in the improvement of the mitochondrial metabolism and oxidative capacity in aged individuals.
线粒体功能的损伤是衰老的一个标志。随着衰老的发生，有两种与线粒体完整性密切相关的机制下调，包括线粒体-核失衡（例如，线粒体编码蛋白与核编码蛋白之间的失衡）和线粒体未折叠蛋白反应（UPRmt）。在这里，我们评估了有氧运动对老年小鼠骨骼肌中线粒体-核失衡和 UPRmt 标志物的影响。我们结合生理测试、分子和生物信息学分析，评估了 4 周有氧运动训练对年轻（2 个月）和老年（24 个月）C57BL/6J 小鼠骨骼肌中线粒体-核失衡和 UPRmt 标志物的影响。最初，我们发现衰老降低了腓肠肌中的几种线粒体基因，并且伴随着 UPRmt 标志物（包括 Yme1l1 和 Clpp mRNA）的低水平。正如预期的那样，体育锻炼改善了老年小鼠的全身代谢和身体表现。有氧运动增加了骨骼肌中线粒体生物发生/功能的关键蛋白（VDAC 和 SIRT1）以及线粒体编码基因（mtNd1、mtCytB 和 mtD-Loop）。有趣的是，有氧运动诱导了线粒体-核失衡，增加了老年小鼠骨骼肌中 MTCO1/ATP5a 比值和 UPRmt 标志物，包括 HSP60、Lonp1 和 Yme1L1 蛋白水平。这些数据表明，有氧运动训练在衰老过程中诱导了骨骼肌中的线粒体-核失衡和 UPRmt。这些现象可能与改善衰老个体的线粒体代谢和氧化能力有关。
