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    597 results match your criteria Hutchinson-Gilford Progeria

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    Metformin decreases progerin expression and alleviates pathological defects of Hutchinson-Gilford progeria syndrome cells.
    NPJ Aging Mech Dis 2016 10;2:16026. Epub 2016 Nov 10.
    INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic Diseases, Corbeil Essonnes, France.
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that causes systemic accelerated aging in children. This syndrome is due to a mutation in the LMNA gene that leads to the production of a truncated and toxic form of lamin A called progerin. Because the balance between the A-type lamins is controlled by the RNA-binding protein SRSF1, we have hypothesized that its inhibition may have therapeutic effects for HGPS. Read More

    Nucleocytoplasmic transport in cells with progerin-induced defective nuclear lamina.
    Biophys Chem 2017 Jun 28. Epub 2017 Jun 28.
    NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Piazza San Silvestro 12, 56127 Pisa, Italy. Electronic address:
    Recent data indicate that nuclear lamina (NL) plays a relevant role in many fundamental cellular functions. The peculiar role of NL in cells is dramatically demonstrated by the Hutchinson-Gilford progeria syndrome (HGPS), an inherited laminopathy that causes premature, rapid aging shortly after birth. In HGPS, a mutant form of Lamin A (progeria) leads to a dysmorphic NL structure, but how this perturbation is transduced into cellular changes is still largely unknown. Read More

    MG132-induced progerin clearance is mediated by autophagy activation and splicing regulation.
    EMBO Mol Med 2017 Jul 3. Epub 2017 Jul 3.
    Aix Marseille Univ, INSERM, GMGF (Génétique Médicale et Génomique Fonctionnelle), Marseille, France
    Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature and accelerated aging disease caused by a de novo point mutation in LMNA encoding A-type lamins. Progerin, a truncated and toxic prelamin A issued from aberrant splicing, accumulates in HGPS cells' nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. Read More

    Elimination of cancer stem cells and reactivation of latent HIV-1 via AMPK activation: Common mechanism of action linking inhibition of tumorigenesis and the potential eradication of HIV-1.
    Med Hypotheses 2017 Jul 31;104:133-146. Epub 2017 May 31.
    Finley BioSciences, 9900 Richmond Avenue, #823, Houston, TX 77042-4539, United States. Electronic address:
    Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure. Read More

    Rare progerin-expressing preadipocytes and adipocytes contribute to tissue depletion over time.
    Sci Rep 2017 Jun 30;7(1):4405. Epub 2017 Jun 30.
    Department of Biosciences and Nutrition, Karolinska Institutet, 14183, Huddinge, Sweden.
    Accumulation of progerin is believed to underlie the pathophysiology of Hutchinson-Gilford progeria syndrome, a disease characterized by clinical features suggestive of premature aging, including loss of subcutaneous white adipose tissue (sWAT). Although progerin has been found in cells and tissues from apparently healthy individuals, its significance has been debated given its low expression levels and rare occurrence. Here we demonstrate that sustained progerin expression in a small fraction of preadipocytes and adipocytes of mouse sWAT (between 4. Read More

    Hutchinson-Gilford Progeria Syndrome: A Premature Aging Disease.
    Mol Neurobiol 2017 Jun 28. Epub 2017 Jun 28.
    Department of Bioinformatics and Biotechnology, Faculty of Basic and Applied Sciences, International Islamic University, Islamabad, Pakistan.
    Progeria is sporadic, very rare, autosomal dominant, deadly childhood disorder. It is one of the progeroid syndromes also known as Hutchinson-Gilford progeria syndrome (HGPS). Aging is a developmental process that begins with fertilization and ends up with death involving a lot of environmental and genetic factors. Read More

    Reprogramming progeria fibroblasts re-establishes a normal epigenetic landscape.
    Aging Cell 2017 Aug 8;16(4):870-887. Epub 2017 Jun 8.
    The Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, K1H 8L6.
    Ideally, disease modeling using patient-derived induced pluripotent stem cells (iPSCs) enables analysis of disease initiation and progression. This requires any pathological features of the patient cells used for reprogramming to be eliminated during iPSC generation. Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature aging disorder caused by the accumulation of the truncated form of Lamin A known as Progerin within the nuclear lamina. Read More

    Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.
    Aging (Albany NY) 2017 May;9(5):1453-1469
    Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Bambino Gesu' Children's Research Hospital, IRCCS, Rome, 00146, Italy.
    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Read More

    Lamin A and microtubules collaborate to maintain nuclear morphology.
    Nucleus 2017 May 30:1-14. Epub 2017 May 30.
    a Department of Cell Biology and Molecular Genetics , University of Maryland , College Park , MD , USA.
    Lamin A (LA) is a critical structural component of the nuclear lamina. Mutations within the LA gene (LMNA) lead to several human disorders, most striking of which is Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disorder. HGPS cells are best characterized by an abnormal nuclear morphology known as nuclear blebbing, which arises due to the accumulation of progerin, a dominant mutant form of LA. Read More

    Progeria: an extremely unusual disorder.
    Skeletal Radiol 2017 Aug 24;46(8):1149-1153. Epub 2017 May 24.
    Department of Radiology, NKPSIMS and Lata Mangeshkar Hospital, Hingana Road, Digdoh Hills, Nagpur, Maharashtra, 440019, India.
    Hutchinson-Gilford progeria syndrome, also known as progeria, is an extremely rare disorder with an incidence rate of 1 in 8 million. It occurs sporadically, and patients suffering from this syndrome usually exhibit premature ageing. It has an autosomal recessive inheritance with a slight male predominance. Read More

    Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL).
    Metabolism 2017 Jun 28;71:213-225. Epub 2017 Mar 28.
    Aix Marseille Univ, INSERM, GMGF, Marseille, France; Department of Medical Genetics, Molecular genetics Laboratory, La Timone Children's Hospital, 264 Rue Saint Pierre, 13005, Marseille, France. Electronic address:
    Background: Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 patients with MDPL have been reported in the literature and among them 14 patients have been characterized at the molecular level. Read More

    Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes.
    FASEB J 2017 May 17. Epub 2017 May 17.
    Department of Biomedical Sciences, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA;
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. Read More

    Progerin-Induced Replication Stress Facilitates Premature Senescence in Hutchinson-Gilford Progeria Syndrome.
    Mol Cell Biol 2017 Jul 29;37(14). Epub 2017 Jun 29.
    Department of Biology, York University, Toronto, Ontario, Canada
    Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutation in LMNA that produces an aberrant lamin A protein, progerin. The accumulation of progerin in HGPS cells leads to an aberrant nuclear morphology, genetic instability, and p53-dependent premature senescence. How p53 is activated in response to progerin production is unknown. Read More

    Expression of progerin does not result in an increased mutation rate.
    Chromosome Res 2017 May 6. Epub 2017 May 6.
    MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
    In the premature ageing disease Hutchinson-Gilford progeria syndrome (HGPS), the underlying genetic defect in the lamin A gene leads to accumulation at the nuclear lamina of progerin-a mutant form of lamin A that cannot be correctly processed. This has been reported to result in defects in the DNA damage response and in DNA repair, leading to the hypothesis that, as in normal ageing and in other progeroid syndromes caused by mutation of genes of the DNA repair and DNA damage response pathways, increased DNA damage may be responsible for the premature ageing phenotypes in HGPS patients. However, this hypothesis is based upon the study of markers of the DNA damage response, rather than measurement of DNA damage per se or the consequences of unrepaired DNA damage-mutation. Read More

    Progerin impairs vascular smooth muscle cell growth via the DNA damage response pathway.
    Oncotarget 2017 May;8(21):34045-34056
    Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
    Mutations of the lamin A gene cause various premature aging syndromes, including Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner syndrome. In HGPS (but not atypical Werner syndrome), extensive loss of vascular smooth muscle cells leads to myocardial infarction with premature death. The underlying mechanisms how single gene mutations can cause various phenotypes are largely unknown. Read More

    Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome.
    Aging Cell 2017 Jun 19;16(3):541-550. Epub 2017 Mar 19.
    Well Aging Research Center, DGIST, Daegu, Korea.
    Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. Read More

    Rejuvenation by Partial Reprogramming of the Epigenome.
    Rejuvenation Res 2017 Apr;20(2):146-150
    1 Regenerative Sciences Institute , Sunnyvale, California.
    Epigenetic variation with age is one of the most important hallmarks of aging. Resetting or repairing the epigenome of aging cells in intact animals may rejuvenate the cells and perhaps the entire organism. In fact, differentiated adult cells, which by definition have undergone some epigenetic changes, are capable of being rejuvenated and reprogrammed to create pluripotent stem cells and viable cloned animals. Read More

    Nuclear lamins and progerin are dispensable for antioxidant Nrf2 response to arsenic and cadmium.
    Cell Signal 2017 May 14;33:69-78. Epub 2017 Feb 14.
    Department of Biological Sciences, North Carolina State University, Campus Box 7633, Raleigh, NC 27695-7633, United States. Electronic address:
    Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Read More

    Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model.
    Small 2017 Apr 17;13(15). Epub 2017 Feb 17.
    Biomaterials Innovation Research Center, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
    Organ-on-a-chip platforms seek to recapitulate the complex microenvironment of human organs using miniaturized microfluidic devices. Besides modeling healthy organs, these devices have been used to model diseases, yielding new insights into pathophysiology. Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease showing accelerated vascular aging, leading to the death of patients due to cardiovascular diseases. Read More

    Metformin alleviates ageing cellular phenotypes in Hutchinson-Gilford progeria syndrome dermal fibroblasts.
    Exp Dermatol 2017 Feb 13. Epub 2017 Feb 13.
    Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
    Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and ageing prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature ageing and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. Read More

    A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus.
    PLoS One 2017 26;12(1):e0169189. Epub 2017 Jan 26.
    Unité de Biologie Fonctionnelle et Adaptative (BFA), CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
    A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes (progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p. Read More

    Temsirolimus Partially Rescues the Hutchinson-Gilford Progeria Cellular Phenotype.
    PLoS One 2016 29;11(12):e0168988. Epub 2016 Dec 29.
    Epigenetics of Aging, Department of Dermatology, TUM school of Medicine, Technical University of Munich (TUM), Garching-Munich, Germany.
    Hutchinson-Gilford syndrome (HGPS, OMIM 176670, a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Lamins help maintain the shape and stability of the nuclear envelope in addition to regulating DNA replication, DNA transcription, proliferation and differentiation. Read More

    Lamins and metabolism.
    Clin Sci (Lond) 2017 Jan;131(2):105-111
    Department of Genetics, The Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Lamins are nuclear intermediate filaments (IFs) with important roles in most nuclear activities, including nuclear organization and cell-cycle progression. Mutations in human lamins cause over 17 different diseases, termed laminopathies. Most of these diseases are autosomal dominant and can be roughly divided into four major groups: muscle diseases, peripheral neuronal diseases, accelerated aging disorders and metabolic diseases including Dunnigan type familial partial lipodystrophy (FLPD), acquired partial lipodystrophy (APL) and autosomal dominant leucodystrophy. Read More

    Comparing lamin proteins post-translational relative stability using a 2A peptide-based system reveals elevated resistance of progerin to cellular degradation.
    Nucleus 2016 Nov;7(6):585-596
    a Department of Cell Biology and Molecular Genetics , University of Maryland College Park , MD , USA.
    Nuclear lamins are the major components of the nuclear lamina at the periphery of the nucleus, supporting the nuclear envelope and participating in many nuclear processes, including DNA replication, transcription and chromatin organization. A group of diseases, the laminopathies, is associated with mutations in lamin genes. One of the most striking cases is Hutchinson-Gilford progeria syndrome (HGPS) which is the consequence of a lamin A dominant negative mutant named progerin. Read More

    A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome.
    J Med Genet 2017 Mar 5;54(3):212-216. Epub 2016 Dec 5.
    Department of Pediatrics, Hasbro Children's Hospital, Providence, Rhode Island, USA.
    Background: Hutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the LMNA gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. Read More

    Loss of H3K9me3 Correlates with ATM Activation and Histone H2AX Phosphorylation Deficiencies in Hutchinson-Gilford Progeria Syndrome.
    PLoS One 2016 1;11(12):e0167454. Epub 2016 Dec 1.
    Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, United States of America.
    Compelling evidence suggests that defective DNA damage response (DDR) plays a key role in the premature aging phenotypes in Hutchinson-Gilford progeria syndrome (HGPS). Studies document widespread alterations in histone modifications in HGPS cells, especially, the global loss of histone H3 trimethylated on lysine 9 (H3K9me3). In this study, we explore the potential connection(s) between H3K9me3 loss and the impaired DDR in HGPS. Read More

    Atomic force microscopy and lamins: A review study towards future, combined investigations.
    Microsc Res Tech 2017 Jan 17;80(1):97-108. Epub 2016 Nov 17.
    Department of Engineering and Architecture, University of Trieste, Via Valerio 6-34127, Trieste, Italy.
    In the last decades, atomic force microscopy (AFM) underwent a rapid and stunning development, especially for studying mechanical properties of biological samples. The numerous discoveries relying to this approach, have increased the credit of AFM as a versatile tool, and potentially eligible as a diagnostic equipment. Meanwhile, it has become strikingly evident that lamins are involved on the onset and development of certain diseases, including cancer, Hutchinson-Gilford progeria syndrome, cardiovascular pathologies, and muscular dystrophy. Read More

    Recent advances in understanding the role of lamins in health and disease.
    F1000Res 2016 19;5:2536. Epub 2016 Oct 19.
    Department of Biochemistry and Molecular Biology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Molecular Microbiology and Immunology, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
    Lamins are major components of the nuclear lamina, a network of proteins that supports the nuclear envelope in metazoan cells. Over the past decade, biochemical studies have provided support for the view that lamins are not passive bystanders providing mechanical stability to the nucleus but play an active role in the organization of the genome and the function of fundamental nuclear processes. It has also become apparent that lamins are critical for human health, as a large number of mutations identified in the gene that encodes for A-type lamins are associated with tissue-specific and systemic genetic diseases, including the accelerated aging disorder known as Hutchinson-Gilford progeria syndrome. Read More

    Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations.
    Proc Natl Acad Sci U S A 2016 Nov 31;113(46):E7250-E7259. Epub 2016 Oct 31.
    Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain;
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. Read More

    Inhibition of late sodium current attenuates ionic arrhythmia mechanism in ventricular myocytes expressing LaminA-N195K mutation.
    Heart Rhythm 2016 Nov 3;13(11):2228-2236. Epub 2016 Aug 3.
    Cellular and Molecular Arrhythmia Research Program, Department of Medicine, University of Wisconsin, Madison, Wisconsin. Electronic address:
    Background: Lamin A and C are nuclear filament proteins encoded by the LMNA gene. Mutations in the LMNA gene cause many congenital diseases known as laminopathies, including Emery-Dreifuss muscular dystrophy, Hutchinson-Gilford progeria syndrome, and familial dilated cardiomyopathy (DCM) with conduction disease. A missense mutation (N195K) in the A-type lamins results in familial DCM and sudden arrhythmic death. Read More

    Anaesthesia and orphan disease: Hutchinson-Gilford progeria syndrome, a case report and summary of previous cases.
    Eur J Anaesthesiol 2016 Nov;33(11):869-872
    From the Department of Anaesthesiology, Pain and Palliative Care Medicine (SJMV, MPH), the Department of Paediatric Endocrinology (HLC) and Department of Oral and Maxillofacial Surgery (WAB), Radboud University Medical Centre, Nijmegen, The Netherlands.

    A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells.
    Sci Rep 2016 Oct 14;6:34798. Epub 2016 Oct 14.
    CECS, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic diseases, 2 rue Henri Desbruères, 91100 Corbeil-Essonnes, France.
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Read More

    Mechanics in human fibroblasts and progeria: Lamin A mutation E145K results in stiffening of nuclei.
    J Mol Recognit 2017 Feb 28;30(2). Epub 2016 Sep 28.
    Biophysics Institute, University of Bremen, 28359, Bremen, Germany.
    The lamina is a filamentous meshwork beneath the inner nuclear membrane that confers mechanical stability to nuclei. The E145K mutation in lamin A causes Hutchinson-Gilford progeria syndrome (HGPS). It affects lamin filament assembly and induces profound changes in the nuclear architecture. Read More

    Interruption of progerin-lamin A/C binding ameliorates Hutchinson-Gilford progeria syndrome phenotype.
    J Clin Invest 2016 Oct 12;126(10):3879-3893. Epub 2016 Sep 12.
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G mutation generates a more accessible splicing donor site than does WT and produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal aged cells. In this study, we determined that progerin binds directly to lamin A/C and induces profound nuclear aberrations. Read More

    The effect of the lamin A and its mutants on nuclear structure, cell proliferation, protein stability, and mobility in embryonic cells.
    Chromosoma 2017 Aug 17;126(4):501-517. Epub 2016 Aug 17.
    Laboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-383, Wroclaw, Poland.
    LMNA gene encodes for nuclear intermediate filament proteins lamin A/C. Mutations in this gene lead to a spectrum of genetic disorders, collectively referred to as laminopathies. Lamin A/C are widely expressed in most differentiated somatic cells but not in early embryos and some undifferentiated cells. Read More

    Antisense-Based Progerin Downregulation in HGPS-Like Patients' Cells.
    Cells 2016 Jul 11;5(3). Epub 2016 Jul 11.
    Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385 Marseille, France.
    Progeroid laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS, OMIM #176670), are premature and accelerated aging diseases caused by defects in nuclear A-type Lamins. Most HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type Lamins. This mutation activates a cryptic splice site leading to the deletion of 50 amino acids at its carboxy-terminal domain, resulting in a truncated and permanently farnesylated Prelamin A called Prelamin A Δ50 or Progerin. Read More

    Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.
    Circulation 2016 Jul;134(2):114-25
    From Departments of Anesthesia (L.B.G., M.E.K., A.A.D., K.L., M.M.G.), Cardiology (L.B.S.), Radiology (R.H.C., V.M.S.), Orthopedics (B.D.S.), Neurology (N.J.U.), Dermatology (M.G.L.), Genetics and Genomics (D.T.M.), Gastroenterology and Nutrition (S.Y.H.), and Hematology Oncology (M.W.K.), and Clinical Translational Study Unit (N.Q.), Boston Children's Hospital and Harvard Medical School, MA; Department of Pediatrics, Hasbro Children's Hospital and Warren Alpert Medical School of Brown University, Providence, RI (L.B.G.); Department of Biostatistics, Boston University School of Public Health and Harvard Clinical Research Institute, MA (J.M., R.B.D., H.S.); Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.G.-H.); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, OH (C.M.G.); Center for Advanced Orthopaedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (A.N.); and Division of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (M.W.K.).
    Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. Read More

    Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations.
    Ageing Res Rev 2017 Jan 29;33:18-29. Epub 2016 Jun 29.
    Andalusian Center for Developmental Biology (CABD), CSIC/Junta de Andalucia/Universidad Pablo de Olavide, Carretera de Utrera, Km 1, 41013 Seville, Spain.
    Products of the LMNA gene, primarily lamin A and C, are key components of the nuclear lamina, a proteinaceous meshwork that underlies the inner nuclear membrane and is essential for proper nuclear architecture. Alterations in lamin A and C that disrupt the integrity of the nuclear lamina affect a whole repertoire of nuclear functions, causing cellular decline. In humans, hundreds of mutations in the LMNA gene have been identified and correlated with over a dozen degenerative disorders, referred to as laminopathies. Read More

    Oocyte activation and latent HIV-1 reactivation: AMPK as a common mechanism of action linking the beginnings of life and the potential eradication of HIV-1.
    Med Hypotheses 2016 Aug 13;93:34-47. Epub 2016 May 13.
    Finley BioSciences, Houston, TX 77042-4539, United States. Electronic address:
    In all mammalian species studied to date, the initiation of oocyte activation is orchestrated through alterations in intracellular calcium (Ca(2+)) signaling. Upon sperm binding to the oocyte plasma membrane, a sperm-associated phospholipase C (PLC) isoform, PLC zeta (PLCζ), is released into the oocyte cytoplasm. PLCζ hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce diacylglycerol (DAG), which activates protein kinase C (PKC), and inositol 1,4,5-trisphosphate (IP3), which induces the release of Ca(2+) from endoplasmic reticulum (ER) Ca(2+) stores. Read More

    Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.
    IUBMB Life 2016 Sep 1;68(9):717-21. Epub 2016 Jul 1.
    Endocrinology and Metabolism Division, National Institute of Nutrition (NIN), Indian Council of Medical Research (ICMR), Hyderabad, 500007, India.
    DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Read More

    Novel LMNA mutations cause an aggressive atypical neonatal progeria without progerin accumulation.
    J Med Genet 2016 Jun 22. Epub 2016 Jun 22.
    Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain.
    Background: Progeroid syndromes are genetic disorders that recapitulate some phenotypes of physiological ageing. Classical progerias, such as Hutchinson-Gilford progeria syndrome (HGPS), are generally caused by mutations in LMNA leading to accumulation of the toxic protein progerin and consequently, to nuclear envelope alterations. In this work, we describe a novel phenotypic feature of the progeria spectrum affecting three unrelated newborns and identify its genetic cause. Read More

    Progeria and the early aging in children: a case report.
    Dermatol Online J 2016 Feb 17;22(2). Epub 2016 Feb 17.
    School of Medicine, Federal University of Parana, Curitiba.
    The Hutchinson-Gilford syndrome or progeria is a rare autosomal dominant syndrome characterized by premature aging and involvement of internal systems, such as the circulatory and locomotor. The diagnosis is essentially clinical and the manifestations become more evident from the first year of life. Long term outcome data from Progeria Research Foundation clinical trials have demonstrated an increase in survival in recent years. Read More

    Repression of the Antioxidant NRF2 Pathway in Premature Aging.
    Cell 2016 Jun;165(6):1361-1374
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal premature aging disorder. The disease is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A, leading, through unknown mechanisms, to diverse morphological, epigenetic, and genomic damage and to mesenchymal stem cell (MSC) attrition in vivo. Using a high-throughput siRNA screen, we identify the NRF2 antioxidant pathway as a driver mechanism in HGPS. Read More

    Dangerous Entrapment for NRF2.
    Cell 2016 Jun;165(6):1312-1313
    Department of Biology, 434 Hutchison Hall, River Campus, University of Rochester, Rochester, NY 14627, USA.
    Progerin, a mutated lamin A, causes the severe premature-aging syndrome Hutchinson-Gilford progeria (HGPS). Kubben et al. present a driving mechanism for HGPS involving trapping of NRF2 at the nuclear periphery by progerin. Read More

    Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells.
    Methods Mol Biol 2016 ;1416:289-98
    Cardiology Division, Department of Medicine, University of Hong Kong, Hong Kong, China.
    Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days. Read More

    Mood, stress and longevity: convergence on ANK3.
    Mol Psychiatry 2016 Aug 24;21(8):1037-49. Epub 2016 May 24.
    Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
    Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. Read More

    The nuclear lamina in health and disease.
    Nucleus 2016 May 9;7(3):233-48. Epub 2016 May 9.
    a Andalusian Center for Developmental Biology (CABD) , CSIC/Junta de Andalucia/Universidad Pablo de Olavide , Seville , Spain.
    The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Read More

    Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes.
    Oncotarget 2016 May;7(21):30018-31
    Edward A. Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St. Louis, MO, USA.
    Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating incurable premature aging disease caused by accumulation of progerin, a toxic lamin A mutant protein. HGPS patient-derived cells exhibit nuclear morphological abnormalities, altered signaling pathways, genomic instability, and premature senescence. Here we uncover new molecular mechanisms contributing to cellular decline in progeria. Read More

    Progerin impairs chromosome maintenance by depleting CENP-F from metaphase kinetochores in Hutchinson-Gilford progeria fibroblasts.
    Oncotarget 2016 Apr;7(17):24700-18
    Epigenetics of Aging, Department of Dermatology, TUM School of Medicine, Technical University Munich (TUM), Garching-Munich, Germany.
    Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke. The most common mutation in HGPS is at position G608G (GGC>GGT) within exon 11 of the LMNA gene. Read More

    Modulation of LMNA splicing as a strategy to treat prelamin A diseases.
    J Clin Invest 2016 Apr 21;126(4):1592-602. Epub 2016 Mar 21.
    The alternatively spliced products of LMNA, lamin C and prelamin A (the precursor to lamin A), are produced in similar amounts in most tissues and have largely redundant functions. This redundancy suggests that diseases, such as Hutchinson-Gilford progeria syndrome (HGPS), that are caused by prelamin A-specific mutations could be treated by shifting the output of LMNA more toward lamin C. Here, we investigated mechanisms that regulate LMNA mRNA alternative splicing and assessed the feasibility of reducing prelamin A expression in vivo. Read More

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