Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Spain.
Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
J Gerontol A Biol Sci Med Sci. 2018 Nov 10;73(12):1594-1601. doi: 10.1093/gerona/gly072.
Dysregulation of tissue renin-angiotensin system (RAS) is involved in oxidative and inflammatory processes observed in major aging-related diseases, including neurodegenerative diseases such as Parkinson's disease (PD). Physical exercise has beneficial effects against aging-related changes, dopaminergic neuron vulnerability, and PD progression. The present study indicates that sedentary aged rats have an increase in activity of the nigral angiotensin (Ang) II/Ang type 1 receptor (AT1) axis (ie, the pro-oxidative pro-inflammatory arm), and a decrease in the activity of the RAS protective arm (ie, Ang II/AT2 and Ang 1-7/Mas receptor axis) in comparison with young rats. In addition, sedentary aged rats showed a decrease in levels of nigral IGF-1, SIRT1, SIRT3, and VEGF. Treadmill running induced a significant increase in levels of IGF-1, SIRT1, SIRT3, and VEGF, as well as an increase in expression of the protective Ang 1-7/Mas axis and inhibition of the Ang II/AT1 axis. The exercise-induced increase in IGF-1 and sirtuins may mediate the effects of exercise on the nigral RAS. However, exercise may induce the increase in VEGF and modulation of RAS activity by different pathways. Exercise, via RAS, contributes to inhibition of the pro-oxidative and proinflammatory state that increase dopaminergic neuron vulnerability and risk of PD with aging.
组织肾素-血管紧张素系统（RAS）的失调与衰老相关疾病中观察到的氧化和炎症过程有关，包括帕金森病（PD）等神经退行性疾病。体育锻炼对衰老相关变化、多巴胺能神经元易损性和 PD 进展具有有益作用。本研究表明，与年轻大鼠相比，久坐的老年大鼠黑质血管紧张素（Ang）II/Ang 型 1 受体（AT1）轴的活性增加（即促氧化促炎臂），而 RAS 保护臂（即 Ang II/AT2 和 Ang 1-7/Mas 受体轴）的活性降低。此外，久坐的老年大鼠黑质 IGF-1、SIRT1、SIRT3 和 VEGF 水平降低。跑步机跑步显著增加了 IGF-1、SIRT1、SIRT3 和 VEGF 的水平，同时增加了保护性 Ang 1-7/Mas 轴的表达，并抑制了 Ang II/AT1 轴。运动引起的 IGF-1 和 Sirtuins 的增加可能介导了运动对黑质 RAS 的影响。然而，运动可能通过不同途径诱导 VEGF 的增加和 RAS 活性的调节。运动通过 RAS 有助于抑制促氧化和促炎状态，从而增加多巴胺能神经元易损性和衰老时 PD 的风险。
