Geriatric Research, Education, and Clinical Center, George E. Whalen Veterans' Affairs Medical Center, Salt Lake City, Utah.
Department of Nutrition and Integrative Physiology, University of Utah Salt Lake City, Utah.
Am J Physiol Regul Integr Comp Physiol. 2020 Apr 1;318(4):R701-R711. doi: 10.1152/ajpregu.00268.2019. Epub 2020 Feb 5.
Recognizing the age-related decline in skeletal muscle feed artery (SMFA) vasodilatory function, this study examined the link between vasodilatory and mitochondrial respiratory function in the human vasculature. Twenty-four SMFAs were harvested from young (35 ± 6 yr, = 9) and old (71 ± 9 yr, = 15) subjects. Vasodilation in SMFAs was assessed, by pressure myography, in response to flow-induced shear stress, acetylcholine (ACh), and sodium nitroprusside (SNP) while mitochondrial respiration was measured, by respirometry, in permeabilized SMFAs. Endothelium-dependent vasodilation was significantly attenuated in the old, induced by both flow (young: 92 ± 3, old: 45 ± 4%) and ACh (young: 92 ± 3, old: 54 ± 5%), with no significant difference in endothelium-independent vasodilation. Complex I and I + II state 3 respiration was significantly lower in the old (CI young: 10.1 ± 0.8, old: 7.0 ± 0.4 pmol·s·mg; CI + II young: 12.3 ± 0.6, old: 7.6 ± 0.4 pmol·s·mg). The respiratory control ratio (RCR) was also significantly attenuated in the old (young: 2.2 ± 0.1, old: 1.1 ± 0.1). Furthermore, state 3 (CI + II) and 4 respiration, as well as RCR, were significantly correlated ( = 0.49-0.86) with endothelium-dependent, but not endothelium-independent, function. Finally, the direct intervention with mitochondrial-targeted antioxidant (MitoQ) significantly improved endothelium-dependent vasodilation in the old but not in the young. Thus, the age-related decline in vasodilatory function is linked to attenuated vascular mitochondrial respiratory function, likely by augmented free radicals. In human skeletal muscle feed arteries, the well-recognized age-related fall in endothelium-dependent vasodilatory function is strongly linked to a concomitant fall in vascular mitochondrial respiratory function. The direct intervention with the mitochondrial-targeted antioxidant restored vasodilatory function in the old but not in the young, supporting the concept that exacerbated mitochondrial-derived free radical production is linked to age-related vasodilatory dysfunction. Age-related vasodilatory dysfunction in humans is linked to attenuated vascular mitochondrial respiratory function, likely a consequence of augmented free radical production.
认识到与年龄相关的骨骼肌营养动脉（SMFA）血管舒张功能下降，本研究检查了人类血管中血管舒张功能和线粒体呼吸功能之间的联系。从年轻（35 ± 6 岁，n = 9）和老年（71 ± 9 岁，n = 15）受试者中采集了 24 个 SMFAs。通过压力肌动描记术评估 SMFAs 对血流诱导的切应力、乙酰胆碱（ACh）和硝普钠（SNP）的血管舒张作用，同时通过呼吸计测量 SMFAs 中通透性的线粒体呼吸作用。在年轻受试者中，由血流（年轻：92 ± 3%，老年：45 ± 4%）和 ACh（年轻：92 ± 3%，老年：54 ± 5%）诱导的内皮依赖性血管舒张明显减弱，而内皮非依赖性血管舒张无显著差异。在老年组中，复合物 I 和 I + II 状态 3 呼吸明显降低（CI 年轻：10.1 ± 0.8，老年：7.0 ± 0.4 pmol·s·mg；CI + II 年轻：12.3 ± 0.6，老年：7.6 ± 0.4 pmol·s·mg）。老年组的呼吸控制比（RCR）也明显降低（年轻：2.2 ± 0.1，老年：1.1 ± 0.1）。此外，状态 3（CI + II）和 4 呼吸以及 RCR 与内皮依赖性但非内皮非依赖性功能显著相关（ = 0.49-0.86）。最后，线粒体靶向抗氧化剂（MitoQ）的直接干预显著改善了老年组的内皮依赖性血管舒张，但对年轻组无改善。因此，血管舒张功能的年龄相关性下降与血管线粒体呼吸功能的减弱有关，这可能是自由基增加的结果。在人类骨骼肌营养动脉中，与年龄相关的公认的内皮依赖性血管舒张功能下降与血管线粒体呼吸功能的下降密切相关。线粒体靶向抗氧化剂的直接干预恢复了老年组的血管舒张功能，但对年轻组无改善，这支持了线粒体衍生自由基产生加剧与与年龄相关的血管舒张功能障碍有关的概念。人类与年龄相关的血管舒张功能障碍与血管线粒体呼吸功能减弱有关，这可能是自由基产生增加的结果。
