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 (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.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Villa-Bellosta Rdoi
10.15252/emmm.202012423subject
Has Abstractpub_date
2020-10-07 00:00:00pages
e12423issue
10eissn
1757-4676issn
1757-4684journal_volume
12pub_type
杂志文章abstract::Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still n...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100136
更新日期:2011-05-01 00:00:00
abstract::Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable cell cycle arrest occurring in response to damage and stress and is considered a hallmark of ageing. Senescent cells accumulate in multiple organs durin...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201810234
更新日期:2019-12-01 00:00:00
abstract::Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors ('inhibitors') seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302859
更新日期:2013-11-01 00:00:00
abstract::The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404838
更新日期:2015-09-01 00:00:00
abstract::Lysosomal storage diseases (LSDs) are a group of genetic disorders due to defects in any aspect of lysosomal biology. During the past two decades, different approaches have been introduced for the treatment of these conditions. Among them, enzyme replacement therapy (ERT) represented a major advance and is used succes...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.200900036
更新日期:2009-08-01 00:00:00
abstract::Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505731
更新日期:2015-11-01 00:00:00
abstract::Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID-19). The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. El...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012421
更新日期:2020-07-07 00:00:00
abstract::Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sust...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201000093
更新日期:2010-09-01 00:00:00
abstract::There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells be...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404353
更新日期:2015-04-01 00:00:00
abstract::Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. He...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607492
更新日期:2017-09-01 00:00:00
abstract::While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505613
更新日期:2016-03-01 00:00:00
abstract::The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in int...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506030
更新日期:2016-08-01 00:00:00
abstract::Sterile inflammation underlies many diseases of the cornea including serious chemical burns and the common dry eye syndrome. In search for therapeutic targets for corneal inflammation, we defined the kinetics of neutrophil infiltration in a model of sterile injury to the cornea and identified molecular and cellular me...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201200221
更新日期:2012-05-01 00:00:00
abstract::The majority of human colorectal cancers (CRCs) are initiated by mutations arising in the adenomatous polyposis coli (APC) tumour suppressor gene. However, a new class of non-APC mutated CRCs has been defined that have a serrated histopathology and carry the (V600E)BRAF oncogene. Here we have investigated the pathogen...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201000099
更新日期:2010-11-01 00:00:00
abstract::In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2-3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.201403876
更新日期:2014-06-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common cause of dementia. There are currently no effective treatments that may delay the onset, slow the progression or prevent the disease. Unless such treatments are developed, the number of AD cases is expected to double in the next 30 years. There is overwhelming genetic and bi...
journal_title:EMBO molecular medicine
pub_type: 评论,杂志文章
doi:10.1002/emmm.200900030
更新日期:2009-07-01 00:00:00
abstract::Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506078
更新日期:2016-06-01 00:00:00
abstract::Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302567
更新日期:2013-10-01 00:00:00
abstract::The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MM...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404402
更新日期:2014-12-01 00:00:00
abstract::Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201403943
更新日期:2014-06-01 00:00:00
abstract::Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced kinase1 (PINK1) are important causes of recessive Parkinson disease (PD). Studies on loss of function and overexpression implicate PINK1 in apoptosis, abnormal mitochondrial morphology, impaired dopamine release and motor deficits. However,...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.200900006
更新日期:2009-05-01 00:00:00
abstract::EMBO Molecular Medicine is enriched by a number of innovative policies designed to enhance the editorial process: peer review process files, de-emphasis of confidential referee comments and cross-refereeing. ...
journal_title:EMBO molecular medicine
pub_type: 社论
doi:10.1002/emmm.201000094
更新日期:2010-09-01 00:00:00
abstract::Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal to...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201438
更新日期:2012-11-01 00:00:00
abstract::Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area com...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506151
更新日期:2016-08-01 00:00:00
abstract::Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview o...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201607485
更新日期:2017-09-01 00:00:00
abstract::The combinations of genetic alterations that cooperate with von Hippel-Lindau (VHL) mutation to cause clear cell renal cell carcinoma (ccRCC) remain poorly understood. We show that the TP53 tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of Vhl and Trp53 in primary mouse embryo...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201202231
更新日期:2013-06-01 00:00:00
abstract::Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404883
更新日期:2015-04-01 00:00:00
abstract::The six transmembrane protein of prostate 2 (STAMP2) is an androgen-regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also s...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404181
更新日期:2015-03-01 00:00:00
abstract::Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing telomerase expressi...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201200212
更新日期:2012-04-01 00:00:00
abstract::Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201809288
更新日期:2019-01-01 00:00:00