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Dietary magnesium supplementation improves lifespan in a mouse model of progeria

ABSTRACT: Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+) 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. LmnaG609G/+ mice also exhibited reduced mitochondrial ATP synthesis secondary to ROS-induced mitochondrial dysfunction. Treatment of LmnaG609G/+ 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 LmnaG609G/+ mice with dietary magnesium improved the proton pumps (complex 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.

SUBMITTER: Dr. Ricardo Villa-Bellosta

PROVIDER: S-SCDT-EMM-2020-12423 | biostudies-other |

REPOSITORIES: biostudies-other

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Dietary magnesium supplementation improves lifespan in a mouse model of progeria.

Project description:Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+ ) 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. LmnaG609G/+ mice also exhibited reduced mitochondrial ATP synthesis secondary to ROS-induced mitochondrial dysfunction. Treatment of LmnaG609G/+ 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 LmnaG609G/+ 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.

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Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model.

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Genetic reduction of mTOR extends lifespan in a mouse model of Hutchinson-Gilford Progeria syndrome.

Project description:Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated aging disorder most notably characterized by cardiovascular disease and premature death from myocardial infarction or stroke. The majority of cases are caused by a de novo single nucleotide mutation in the LMNA gene that activates a cryptic splice donor site, resulting in production of a toxic form of lamin A with a 50 amino acid internal deletion, termed progerin. We previously reported the generation of a transgenic murine model of progeria carrying a human BAC harboring the common mutation, G608G, which in the single-copy state develops features of HGPS that are limited to the vascular system. Here, we report the phenotype of mice bred to carry two copies of the BAC, which more completely recapitulate the phenotypic features of HGPS in skin, adipose, skeletal, and vascular tissues. We further show that genetic reduction of the mechanistic target of rapamycin (mTOR) significantly extends lifespan in these mice, providing a rationale for pharmacologic inhibition of the mTOR pathway in the treatment of HGPS.

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Dietary supplementation with <i>Ceriporia lacerata</i> improves learning and memory in a scopolamine-induced amnesia mouse model.

Project description:Ceriporia lacerata (CL) is a species of white rot fungi. In this study, we have examined the beneficial effect of CL on scopolamine-induced memory impairment in mice. A freeze-dried CL mycelial culture broth was dissolved and orally administered to scopolamine-treated C57BL/6J mice followed by behavioral tests using the Y-maze, passive avoidance, and Morris water maze tasks. CL administration at a daily dose of 200 mg/kg body weight resulted in restoration of exploration reduction and improvement of associative and spatial learning and memory impairment in scopolamine-treated mice. Concomitantly, heme oxygenase-1 was highly expressed in the hippocampal region of CL-administered mice. Moreover, the ethanolic extract of CL significantly increased the transcriptional activity of antioxidant response element and attenuated the glutamate-induced cytotoxicity in HT22 mouse hippocampal neuronal cells. These findings suggest that the CL intake can confer a beneficial effect on learning and memory presumably through protecting hippocampal neuronal cells from oxidative stress-induced damage.Supplementary informationThe online version contains supplementary material available at 10.1007/s10068-021-00945-5.

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Magnesium supplementation improves diabetic mitochondrial and cardiac diastolic function.

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Dietary magnesium supplementation inhibits abdominal vascular calcification in an experimental animal model of chronic kidney disease.

Project description:BackgroundVascular calcification is a key process involved in cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Magnesium supplementation may counteract vascular calcification. In this study we aimed to determine whether increased dietary magnesium intake inhibits vascular calcification in CKD in vivo and explore the mechanisms underlying these effects.MethodsSprague Dawley rats were partially nephrectomized and fed a diet with high phosphate and either high or normal magnesium content for 16 weeks. The primary outcome was the tissue calcium content of the aorta in the high versus normal dietary magnesium group. In addition, we analysed plasma mineral concentrations, aortic vascular calcification identified with von Kossa staining, calcium apposition time and aortic expression of genes related to vascular calcification.ResultsThe number of animals in the highest tissue calcium content tertile was significantly lower in the abdominal aorta [1 (10%) versus 6 (55%); P = .03] in the high versus normal dietary magnesium group, but did not differ in the aortic arch and thoracic aorta. Von Kossa staining and calcium apposition time corresponded to these results. The median tissue calcium content was not significantly different between the groups. Serum phosphate concentrations and expression of osteogenic markers in the aorta did not differ between the groups.ConclusionsThis study demonstrates that increased dietary magnesium inhibits abdominal vascular calcification in an experimental animal model of CKD in vivo. These are promising results for CKD patients and further study is needed to identify the mechanisms involved and to determine the clinical relevance in patients.

| S-EPMC9130027 | biostudies-literature

Boosting ATM activity alleviates ageing and extends lifespan in a mouse model of progeria.

Project description:Protein deacetylase SIRT6 and protein kinase ATM both decline during aging, which are of importance in regualtion of glucose metabolism . To explore the mechnisms of SIRT6 and ATM in glycolysis, we analysed the gene expressions in murine embryonic fibroblast cells generated from wildtype, Sirt6-/-, or Atm-/- mice.

2018-05-05 | GSE109280 | GEO

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