Luo Li, Dai Jia-Ru, Guo Shan-Shan, Lu A-Ming, Gao Xiao-Fang, Gu Yan-Rong, Zhang Xiao-Fei, Xu Hai-Dong, Wang Yan, Zhu Zhou, Wood Lisa J, Qin Zheng-Hong
School of Physical Education and Sports Science.
Department of Pharmacology and Laboratory of Aging and Nervous Diseases (SZS0703), Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, China.
J Gerontol A Biol Sci Med Sci. 2017 Oct 1;72(10):1342-1351. doi: 10.1093/gerona/glw242.
Exercise improves cognitive function in older adults, but the underlying mechanism is largely unknown. Both lysosomal degradation and mitochondrial quality control decline with age. We hypothesized that exercise ameliorates age-related cognitive decline through the improvement of mitochondrial quality control in aged hippocampus, and this effect is associated with lysosomal proteolysis. Sixteen to eighteen-month old male Sprague Dawley rats underwent swim exercise training for 10 weeks. The exercise regimen prevented cognitive decline in aged rats, reduced oxidative stress, and rejuvenated mitochondria in the aged hippocampus. Exercise training promoted mitochondrial biogenesis, increased mitochondrial fusion and fission, and activated autophagy/mitophagy in aged hippocampal neurons. Lysosomal inhibitor chloroquine partly blocked beneficial effects of exercise on cognitive function, oxidative stress, autophagy/mitophagy, and mitochondrial quality control in aged rats. These results suggest that preservation of cognitive function by long-term exercise is associated with improvement of mitochondrial quality control in aged hippocampus and that lysosomal degradation is required for this process. Our findings suggest that exercise training or pharmacological regulation of mitochondrial quality control and lysosomal degradation may be effective strategies for slowing down age-related cognitive decline.
运动可改善老年人的认知功能，但其潜在机制 largely 未知。随着年龄增长，溶酶体降解和线粒体质量控制均会下降。我们推测，运动通过改善老年海马体中的线粒体质量控制来减轻与年龄相关的认知衰退，且这种效应与溶酶体蛋白水解有关。16至18月龄的雄性Sprague Dawley大鼠进行了为期10周的游泳运动训练。该运动方案可预防老年大鼠的认知衰退，减轻氧化应激，并使老年海马体中的线粒体恢复活力。运动训练促进了线粒体生物合成，增加了线粒体融合与裂变，并激活了老年海马神经元中的自噬/线粒体自噬。溶酶体抑制剂氯喹部分阻断了运动对老年大鼠认知功能、氧化应激、自噬/线粒体自噬及线粒体质量控制的有益作用。这些结果表明，长期运动对认知功能的保护与老年海马体中线粒体质量控制的改善有关，且该过程需要溶酶体降解。我们的研究结果表明，运动训练或对线粒体质量控制和溶酶体降解进行药理学调节可能是减缓与年龄相关的认知衰退的有效策略。
