Journal
EMBO MOLECULAR MEDICINE
Volume 12, Issue 10, Pages -Publisher
WILEY
DOI: 10.15252/emmm.202012423
Keywords
aging; HGPS; magnesium; progeria; vascular calcification
Categories
Funding
- Progeria Research Foundation from USA [PRF-2016-68]
- Spanish Ministerio de Economia y Competitividad [SAF-2014-60669-JIN]
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Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (Lmna(G609G/+)) 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(G609G/+)mice also exhibited reduced mitochondrial ATP synthesis secondary to ROS-induced mitochondrial dysfunction. Treatment ofLmna(G609G/+)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 ofLmna(G609G/+)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 cellsin vitroandin vivo,and improved the longevity of mice. This antioxidant property of magnesium may be beneficial in children with HGPS.
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