Cordeiro André Victor, Peruca Guilherme Francisco, Braga Renata Rosseto, Brícola Rafael Santos, Lenhare Luciene, Silva Vagner Ramon Rodrigues, Anaruma Chadi Pellegrini, Katashima Carlos Kiyoshi, Crisol Barbara Moreira, Barbosa Lucas Torres, Simabuco Fernando Moreira, da Silva Adelino Sanchez Ramos, Cintra Dennys Esper, de Moura Leandro Pereira, Pauli José Rodrigo, Ropelle Eduardo Rochete
Laboratory of Molecular Biology of Exercise, University of Campinas, Limeira, SP, Brazil.
Department of Physical Education, Institute of Biosciences, São Paulo State University, Rio Claro, SP, Brazil.
Geroscience. 2021 Jun;43(3):1513-1518. doi: 10.1007/s11357-020-00246-5. Epub 2020 Jul 31.
The impairment of mitochondrial metabolism is a hallmark of aging. Mitonuclear imbalance and the mitochondrial unfolded protein response (UPRmt) are two conserved mitochondrial mechanisms that play critical roles in ensuring mitochondrial proteostasis and function. Here, we combined bioinformatics, physiological, and molecular analyses to examine the role of mitonuclear imbalance and UPRmt in the skeletal muscle of aged rodents and humans. The analysis of transcripts from the skeletal muscle of aged humans (60-70 years old) revealed that individuals with higher levels of UPRmt-related genes displayed a consistent increase in several mitochondrial-related genes, including the OXPHOS-associated genes. Interestingly, high-intensity interval training (HIIT) was effective in stimulating the mitonuclear imbalance and UPRmt in the skeletal muscle of aged mice. Furthermore, these results were accompanied by higher levels of several mitochondrial markers and improvements in physiological parameters and physical performance. These data indicate that the maintenance or stimulation of the mitonuclear imbalance and UPRmt in the skeletal muscle could ensure mitochondrial proteostasis during aging, revealing new insights into targeting mitochondrial metabolism by using physical exercise.
线粒体代谢受损是衰老的一个标志。线粒体-核失衡和线粒体未折叠蛋白反应（UPRmt）是两种保守的线粒体机制，在确保线粒体蛋白质稳态和功能方面发挥着关键作用。在这里，我们结合生物信息学、生理学和分子分析，研究线粒体-核失衡和UPRmt在老年啮齿动物和人类骨骼肌中的作用。对老年人类（60-70岁）骨骼肌转录本的分析表明，UPRmt相关基因水平较高的个体，包括与氧化磷酸化相关的基因在内的几个线粒体相关基因呈现出持续增加。有趣的是，高强度间歇训练（HIIT）能有效刺激老年小鼠骨骼肌中的线粒体-核失衡和UPRmt。此外，这些结果伴随着几种线粒体标志物水平的升高以及生理参数和身体机能的改善。这些数据表明，维持或刺激骨骼肌中的线粒体-核失衡和UPRmt可以在衰老过程中确保线粒体蛋白质稳态，为通过体育锻炼靶向线粒体代谢揭示了新的见解。
