Fundación Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
EMBO Mol Med. 2020 Oct 7;12(10):e12423. doi: 10.15252/emmm.202012423. Epub 2020 Aug 16.
Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (Lmna ) showed an increased level of mitochondrial reactive oxygen species (ROS) and a reduced basal antioxidant capacity, including loss of the NADPH-coupled glutathione redox system. Lmna mice also exhibited reduced mitochondrial ATP synthesis secondary to ROS-induced mitochondrial dysfunction. Treatment of Lmna vascular smooth muscle cells with magnesium-enriched medium improved the intracellular ATP level, enhanced the antioxidant capacity, and thereby reduced mitochondrial ROS production. Moreover, treatment of Lmna mice with dietary magnesium improved the proton pumps (complexes I, III, and IV), stimulated extramitochondrial NADH oxidation and enhanced the coupled mitochondrial membrane potential, and thereby increased H -coupled mitochondrial NADPH and ATP synthesis, which is necessary for cellular energy supply and survival. Consistently, magnesium treatment reduced calcification of vascular smooth muscle cells in vitro and in vivo, and improved the longevity of mice. This antioxidant property of magnesium may be beneficial in children with HGPS.
根据衰老的氧化还原理论，衰老是与氧化还原失衡有关的。一致地，过早衰老的小鼠模型（Lmna）显示线粒体活性氧（ROS）水平增加，基础抗氧化能力降低，包括 NADPH 偶联谷胱甘肽氧化还原系统的丧失。Lmna 小鼠还表现出由于 ROS 诱导的线粒体功能障碍导致的线粒体 ATP 合成减少。用富含镁的培养基处理 Lmna 血管平滑肌细胞可以提高细胞内 ATP 水平，增强抗氧化能力，从而减少线粒体 ROS 的产生。此外，用饮食镁治疗 Lmna 小鼠可以改善质子泵（复合物 I、III 和 IV），刺激细胞外 NADH 氧化并增强偶联的线粒体膜电位，从而增加 H 偶联的线粒体 NADPH 和 ATP 合成，这是细胞能量供应和存活所必需的。一致地，镁处理减少了体外和体内血管平滑肌细胞的钙化，并延长了小鼠的寿命。镁的这种抗氧化特性在患有 HGPS 的儿童中可能是有益的。
