682 results match your criteria Hutchinson-Gilford Progeria


Telomere elongation through hTERT immortalisation leads to chromosome repositioning in control cells and genomic instability in Hutchinson-Gilford Progeria syndrome fibroblasts, expressing a novel SUN1 isoform.

Genes Chromosomes Cancer 2018 Nov 26. Epub 2018 Nov 26.

Genome Engineering and Maintenance Network, Institute for Environment, Health and Societies, Brunel University London, Uxbridge.

Immortalising primary cells with hTERT has been common practice to enable primary cells to be of extended use in the laboratory since they avoid replicative senescence. Studying exogenously expressed hTERT in cells also affords scientists models of early carcinogenesis and telomere behaviour. Control and the premature ageing disease - Hutchinson-Gilford Progeria Syndrome primary dermal fibroblasts, with and without the classical G608G mutation have been immortalised with exogenous hTERT. Read More

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November 2018
7 Reads

Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations.

Hum Genet 2018 Dec 19;137(11-12):921-939. Epub 2018 Nov 19.

Warren Alpert Medical School of Brown University, Providence, RI, USA.

Juvenile segmental progeroid syndromes are rare, heterogeneous disorders characterized by signs of premature aging affecting more than one tissue or organ starting in childhood. Hutchinson-Gilford progeria syndrome (HGPS), caused by a recurrent de novo synonymous LMNA mutation resulting in aberrant splicing and generation of a mutant product called progerin, is a prototypical example of such disorders. Here, we performed a joint collaborative study using massively parallel sequencing and targeted Sanger sequencing, aimed at delineating the underlying genetic cause of 14 previously undiagnosed, clinically heterogeneous, non-LMNA-associated juvenile progeroid patients. Read More

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December 2018
2 Reads
4.824 Impact Factor

Postmitotic cell longevity-associated genes: a transcriptional signature of postmitotic maintenance in neural tissues.

Neurobiol Aging 2018 Oct 19;74:147-160. Epub 2018 Oct 19.

School of Life Sciences, University of Lincoln, Lincoln, UK. Electronic address:

Different cell types have different postmitotic maintenance requirements. Nerve cells, however, are unique in this respect as they need to survive and preserve their functional complexity for the entire lifetime of the organism, and failure at any level of their supporting mechanisms leads to a wide range of neurodegenerative conditions. Whether these differences across tissues arise from the activation of distinct cell type-specific maintenance mechanisms or the differential activation of a common molecular repertoire is not known. Read More

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October 2018
5 Reads

Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse.

J Clin Invest 2018 Nov 13. Epub 2018 Nov 13.

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder characterized by accelerated cardiovascular disease with extensive fibrosis. It is caused by a mutation in LMNA leading to expression of truncated prelamin A (progerin) in the nucleus. To investigate the contribution of the endothelium to cardiovascular HGPS pathology, we generated an endothelium-specific HGPS mouse model with selective endothelial progerin expression. Read More

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November 2018
5 Reads

HiPLA: High-throughput imaging proximity ligation assay.

Methods 2018 Nov 10. Epub 2018 Nov 10.

Cell Biology of Genomes Group, National Cancer Institute, NIH, Building 41, 41 Library Drive, Bethesda, MD 20892, USA. Electronic address:

Protein-protein interactions are essential for cellular structure and function. To delineate how the intricate assembly of protein interactions contribute to cellular processes in health and disease, new methodologies that are both highly sensitive and can be applied at large scale are needed. Here, we develop HiPLA (high-throughput imaging proximity ligation assay), a method that employs the well-established antibody-based proximity ligation assay in a high-throughput imaging screening format as a novel means to systematically visualize protein interactomes. Read More

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November 2018
3 Reads

BK channel overexpression on plasma membrane of fibroblasts from Hutchinson-Gilford progeria syndrome.

Aging (Albany NY) 2018 Nov;10(11):3148-3160

Department of Physics and Astronomy (D.I.F.A.) University of Bologna, Bologna, Italy.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. It is a genetic condition that occurs due to a mutation in the gene encoding for the nuclear structural protein lamin A. The lamin family of proteins are thought to be involved in nuclear stability, chromatin structure and gene expression and this leads to heavy effects on the regulation and functionality of the cell machinery. Read More

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November 2018
5 Reads

Next-Generation Sequencing and Quantitative Proteomics of Hutchinson-Gilford progeria syndrome-derived cells point to a role of nucleotide metabolism in premature aging.

PLoS One 2018 31;13(10):e0205878. Epub 2018 Oct 31.

Grupo de Terapia Celular y Medicina Regenerativa, Dpto. Ciencias Biomédicas, Medicina y Fisioterapia, Facultad de Ciencias de la Salud, Universidade da Coruña, INIBIC-CHUAC.

Hutchinson-Gilford progeria syndrome (HGPS) is a very rare fatal disease characterized for accelerated aging. Although the causal agent, a point mutation in LMNA gene, was identified more than a decade ago, the molecular mechanisms underlying HGPS are still not fully understood and, currently, there is no cure for the patients, which die at a mean age of thirteen. With the aim of unraveling non-previously altered molecular pathways in the premature aging process, human cell lines from HGPS patients and from healthy parental controls were studied in parallel using Next-Generation Sequencing (RNAseq) and High-Resolution Quantitative Proteomics (iTRAQ) techniques. Read More

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October 2018

JH-4 reduces HMGB1-mediated septic responses and improves survival rate in septic mice.

J Cell Biochem 2018 Oct 30. Epub 2018 Oct 30.

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu, Republic of Korea.

Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as attractive therapeutic strategies for the management of severe vascular inflammatory diseases. Recently, we found that JH-4, a synthesized decursin derivative, exhibited a strong anti-Hutchinson-Gilford progeria syndrome by efficiently blocking progerin-lamin A/C binding. In this study, we examined the effects of JH-4 on HMGB1-mediated septic responses and the survival rate in a mouse sepsis model. Read More

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October 2018
3 Reads

Expression of the Hutchinson-Gilford Progeria Mutation Leads to Aberrant Dentin Formation.

Sci Rep 2018 Oct 18;8(1):15368. Epub 2018 Oct 18.

Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju, 54896, South Korea.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated senescence disease, manifesting dental abnormalities and several symptoms suggestive of premature aging. Although irregular secondary dentin formation in HGPS patients has been reported, pathological mechanisms underlying aberrant dentin formation remain undefined. In this study, we analyzed the mandibular molars of a tissue-specific mouse model that overexpresses the most common HGPS mutation (LMNA, c. Read More

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October 2018
1 Read

Endothelial Nuclear Lamina in Mechanotransduction Under Shear Stress.

Authors:
Julie Y Ji

Adv Exp Med Biol 2018 ;1097:83-104

Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA.

Endothelial cells that line the lumen of blood vessels are at the interface between hemodynamic forces and vascular wall biology. Endothelial cells transduce mechanical and biological signals from blood flow into intracellular signaling cascades through a process called mechanotransduction. Mechanotransduction is an important part of normal cell functions, as well as endothelial dysfunction which leads to inflammation and pathological conditions. Read More

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January 2018
2 Reads

Methionine restriction for improving progeria: another autophagy-inducing anti-aging strategy?

Autophagy 2018 Oct 10. Epub 2018 Oct 10.

c Gustave Roussy Cancer Campus , Villejuif , France.

Methionine restriction, i.e., a partial depletion of the essential sulfur amino acid methionine from nutrition, extends lifespan in model organisms including yeast, nematodes, mice and rats. Read More

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October 2018
5 Reads

Forced expression of mouse progerin attenuates the osteoblast differentiation interrupting β-catenin signal pathway in vitro.

Cell Tissue Res 2018 Oct 3. Epub 2018 Oct 3.

Department of Anatomy, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan.

Nuclear protein, lamin A, which is a component of inner membrane on nucleoplasm, plays a role in nuclear formation and cell differentiation. The expression of mutated lamin A, termed progerin, causes a rare genetic aging disorder, Hutchinson-Gilford progeria syndrome, which shows abnormal bone formation with the decrease in a number of osteoblasts and osteocytes. However, exact molecular mechanism how progerin exerts depressive effects on osteogenesis has not been fully understood. Read More

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October 2018

Disrupting the LINC complex in smooth muscle cells reduces aortic disease in a mouse model of Hutchinson-Gilford progeria syndrome.

Sci Transl Med 2018 Sep;10(460)

Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Hutchinson-Gilford progeria syndrome is a disorder of premature aging in children caused by de novo mutations in that lead to the synthesis of an internally truncated form of prelamin A (commonly called progerin). The production of progerin causes multiple disease phenotypes, including an unusual vascular phenotype characterized by the loss of smooth muscle cells in the arterial media and fibrosis of the adventitia. We show that progerin expression, combined with mechanical stress, promotes smooth muscle cell death. Read More

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September 2018
1 Read

Targeting the phospholipase A2 receptor ameliorates premature aging phenotypes.

Aging Cell 2018 Dec 14;17(6):e12835. Epub 2018 Sep 14.

Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.

Hutchinson-Gilford progeria syndrome (HGPS) is a lethal premature aging that recapitulates many normal aging characteristics. This disorder is caused by mutation in the LMNA gene leading to the production of progerin which induces misshapen nuclei, cellular senescence, and aging. We previously showed that the phospholipase A2 receptor (PLA2R1) promotes senescence induced by replicative, oxidative, and oncogenic stress but its role during progerin-induced senescence and in progeria is currently unknown. Read More

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December 2018
2 Reads

Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism.

Cell Rep 2018 Aug;24(9):2392-2403

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Electronic address:

Dietary intervention constitutes a feasible approach for modulating metabolism and improving the health span and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Read More

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August 2018
9 Reads

Epigenetic clocks galore: a new improved clock predicts age-acceleration in Hutchinson Gilford Progeria Syndrome patients.

Aging (Albany NY) 2018 Aug;10(8):1799-1800

CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

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August 2018
2 Reads

Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS.

Aging Cell 2018 Oct 15;17(5):e12824. Epub 2018 Aug 15.

CNR Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy.

Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson-Gilford progeria, a severe LMNA-linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. Read More

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October 2018
2 Reads

Chemical screen identifies a geroprotective role of quercetin in premature aging.

Protein Cell 2018 Aug 1. Epub 2018 Aug 1.

Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China.

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Read More

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August 2018
10 Reads
2.850 Impact Factor

Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and studies.

Aging (Albany NY) 2018 Jul;10(7):1758-1775

Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 0RQ, United Kingdom.

DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. Read More

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July 2018
2 Reads

Electrocardiographic Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome-Reply.

JAMA Cardiol 2018 Oct;3(10):1025

Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.

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October 2018
1 Read

Electrocardiographic Abnormalities in Patients With Hutchinson-Gilford Progeria Syndrome.

JAMA Cardiol 2018 Oct;3(10):1024-1025

Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Madrid, Spain.

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October 2018

Transposable elements, placental development, and oocyte activation: Cellular stress and AMPK links jumping genes with the creation of human life.

Authors:
Jahahreeh Finley

Med Hypotheses 2018 Sep 19;118:44-54. Epub 2018 May 19.

Finley BioSciences, Houston, TX 77042-4539, United States. Electronic address:

Transposable elements (TEs), also known as "jumping genes", are DNA sequences first described by Nobel laureate Barbara McClintock that comprise nearly half of the human genome and are able to transpose or move from one genomic location to another. As McClintock also noted that a genome "shock" or stress may induce TE activation and transposition, accumulating evidence suggests that cellular stress (e.g. Read More

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September 2018
20 Reads

Cellular stress and AMPK activation as a common mechanism of action linking the effects of metformin and diverse compounds that alleviate accelerated aging defects in Hutchinson-Gilford progeria syndrome.

Authors:
Jahahreeh Finley

Med Hypotheses 2018 Sep 28;118:151-162. Epub 2018 Jun 28.

Finley BioSciences, Houston, TX 77042-4539, United States. Electronic address:

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by an accelerated aging phenotype that typically leads to death via stroke or myocardial infarction at approximately 14.6 years of age. Most cases of HGPS have been linked to the extensive use of a cryptic splice donor site located in the LMNA gene due to a de novo mutation, generating a truncated and toxic protein known as progerin. Read More

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September 2018
2 Reads

EFFECTIVE PAIN CONTROL IN HUTCHINSON-GILFORD PROGERIA SYNDROME.

Innov Clin Neurosci 2018 Jun;15(5-6):11-12

Dr. Majeed is an attending psychiatrist with Department of Psychiatry, Natchaug Hospital in Norwich, Connecticut.

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June 2018
6 Reads

Erythrocyte Senescence in a Model of Rat Displaying Hutchinson-Gilford Progeria Syndrome.

Anal Cell Pathol (Amst) 2018 29;2018:5028925. Epub 2018 May 29.

Department of Biochemistry, University of Allahabad, Allahabad 211002, India.

Background: Increased oxidative stress is a major cause of aging and age-related diseases. Erythrocytes serve as good model for aging studies. Dihydrotachysterol is known to induce premature aging feature in rats mimicking Hutchinson-Gilford progeria syndrome. Read More

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October 2018
2 Reads

Diminished Canonical β-Catenin Signaling During Osteoblast Differentiation Contributes to Osteopenia in Progeria.

J Bone Miner Res 2018 Nov 1;33(11):2059-2070. Epub 2018 Aug 1.

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA.

Patients with Hutchinson-Gilford progeria syndrome (HGPS) have low bone mass and an atypical skeletal geometry that manifests in a high risk of fractures. Using both in vitro and in vivo models of HGPS, we demonstrate that defects in the canonical WNT/β-catenin pathway, seemingly at the level of the efficiency of nuclear import of β-catenin, impair osteoblast differentiation and that restoring β-catenin activity rescues osteoblast differentiation and significantly improves bone mass. Specifically, we show that HGPS patient-derived iPSCs display defects in osteoblast differentiation, characterized by a decreased alkaline phosphatase activity and mineralizing capacity. Read More

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November 2018

Inhibition of the acetyltransferase NAT10 normalizes progeric and aging cells by rebalancing the Transportin-1 nuclear import pathway.

Sci Signal 2018 Jul 3;11(537). Epub 2018 Jul 3.

The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, University of Cambridge, CB2 1QN, UK.

Hutchinson-Gilford progeria syndrome (HGPS) is an incurable premature aging disease. Identifying deregulated biological processes in HGPS might thus help define novel therapeutic strategies. Fibroblasts from HGPS patients display defects in nucleocytoplasmic shuttling of the GTP-bound form of the small GTPase Ran (RanGTP), which leads to abnormal transport of proteins into the nucleus. Read More

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July 2018
1 Read

Genomic instability and DNA replication defects in progeroid syndromes.

Nucleus 2018 Dec 23;9(1):368-379. Epub 2018 Jun 23.

a Dipartimento di Biologia e Biotecnologie "C. Darwin" , Sapienza Università di Roma , Roma , Italy.

Progeroid syndromes induced by mutations in lamin A or in its interactors - named progeroid laminopathies - are model systems for the dissection of the molecular pathways causing physiological and premature aging. A large amount of data, based mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best characterized progeroid laminopathy, has highlighted the role of lamins in multiple DNA activities, including replication, repair, chromatin organization and telomere function. On the other hand, the phenotypes generated by mutations affecting genes directly acting on DNA function, as mutations in the helicases WRN and BLM or in the polymerase polδ, share many of the traits of progeroid laminopathies. Read More

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December 2018
1 Read

Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts.

Geroscience 2018 Jun 21. Epub 2018 Jun 21.

Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, 19102, USA.

Inhibition of mTOR signaling using rapamycin has been shown to increase lifespan and healthspan in multiple model organisms; however, the precise mechanisms for the beneficial effects of rapamycin remain uncertain. We have previously reported that rapamycin delays senescence in human cells and that enhanced mitochondrial biogenesis and protection from mitochondrial stress is one component of the benefit provided by rapamycin treatment. Here, using two models of senescence, replicative senescence and senescence induced by the presence of the Hutchinson-Gilford progeria lamin A mutation, we report that senescence is accompanied by elevated glycolysis and increased oxidative phosphorylation, which are both reduced by rapamycin. Read More

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June 2018
1 Read

Farnesyltransferase inhibitor and rapamycin correct aberrant genome organisation and decrease DNA damage respectively, in Hutchinson-Gilford progeria syndrome fibroblasts.

Biogerontology 2018 Dec 15;19(6):579-602. Epub 2018 Jun 15.

Progeria Research Team, Healthy Ageing Theme, Institute for Environment, Health and Societies, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, UB8 3PH, UK.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal premature ageing disease in children. HGPS is one of several progeroid syndromes caused by mutations in the LMNA gene encoding the nuclear structural proteins lamins A and C. In classic HGPS the mutation G608G leads to the formation of a toxic lamin A protein called progerin. Read More

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December 2018
8 Reads

Pathological modelling of pigmentation disorders associated with Hutchinson-Gilford Progeria Syndrome (HGPS) revealed an impaired melanogenesis pathway in iPS-derived melanocytes.

Sci Rep 2018 Jun 14;8(1):9112. Epub 2018 Jun 14.

CECS, I-Stem, Corbeil-Essonnes, 91100, France.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder that leads to premature aging. In this study, we used induced pluripotent stem cells to investigate the hypopigmentation phenotypes observed in patients with progeria. Accordingly, two iPS cell lines were derived from cells from HGPS patients and differentiated into melanocytes. Read More

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June 2018
3 Reads

Facilitation of hippocampal long-term potentiation and reactivation of latent HIV-1 via AMPK activation: Common mechanism of action linking learning, memory, and the potential eradication of HIV-1.

Authors:
Jahahreeh Finley

Med Hypotheses 2018 Jul 22;116:61-73. Epub 2018 Apr 22.

Finley BioSciences, 9900 Richmond Avenue, Houston, TX 77042-4539, United States. Electronic address:

Learning and memory are generally considered the behavioral correlates of long-term potentiation (LTP), a form of synaptic plasticity associated with a persistent and long-lasting increase in synaptic strength. Repetitive stimulation of excitatory synapses in the hippocampal CA1 region leads to release and binding of glutamate to the glutamate receptors AMPAR and NMDAR located on pyramidal neurons. Activation of AMPARs facilitates Na influx, postsynaptic depolarization, NMDAR-mediated Ca influx, and activation of several intracellular mechanisms that characterize LTP, including increased AMPAR synthesis, ROS production, and ER Ca release. Read More

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July 2018
1 Read

Lamins and bone disorders: current understanding and perspectives.

Oncotarget 2018 Apr 27;9(32):22817-22831. Epub 2018 Apr 27.

CNR Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy.

Lamin A/C is a major constituent of the nuclear lamina implicated in a number of genetic diseases, collectively known as laminopathies. The most severe forms of laminopathies feature, among other symptoms, congenital scoliosis, osteoporosis, osteolysis or delayed cranial ossification. Importantly, specific bone districts are typically affected in laminopathies. Read More

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April 2018
2 Reads

missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or protein stability.

Dis Model Mech 2018 07 13;11(7). Epub 2018 Jul 13.

Department of Cell Biology, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA

The human zinc metalloprotease ZMPSTE24 is an integral membrane protein crucial for the final step in the biogenesis of the nuclear scaffold protein lamin A, encoded by After farnesylation and carboxyl methylation of its C-terminal CAAX motif, the lamin A precursor (prelamin A) undergoes proteolytic removal of its modified C-terminal 15 amino acids by ZMPSTE24. Mutations in or that impede this prelamin A cleavage step cause the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS), and the related progeroid disorders mandibuloacral dysplasia type B (MAD-B) and restrictive dermopathy (RD). Here, we report the development of a 'humanized yeast system' to assay ZMPSTE24-dependent cleavage of prelamin A and examine the eight known disease-associated missense mutations. Read More

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July 2018
1 Read

Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome.

JAMA 2018 04;319(16):1687-1695

Division of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Importance: Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare fatal premature aging disease. There is no approved treatment.

Objective: To evaluate the association of monotherapy using the protein farnesyltransferase inhibitor lonafarnib with mortality rate in children with HGPS. Read More

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April 2018
1 Read

Precision Medicine and Progress in the Treatment of Hutchinson-Gilford Progeria Syndrome.

JAMA 2018 04;319(16):1663-1664

Department of Pathology, University of Washington, Seattle.

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April 2018
2 Reads

Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome.

Nat Commun 2018 04 27;9(1):1700. Epub 2018 Apr 27.

The Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QN, UK.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, but devastating genetic disease characterized by segmental premature aging, with cardiovascular disease being the main cause of death. Cells from HGPS patients accumulate progerin, a permanently farnesylated, toxic form of Lamin A, disrupting the nuclear shape and chromatin organization, leading to DNA-damage accumulation and senescence. Therapeutic approaches targeting farnesylation or aiming to reduce progerin levels have provided only partial health improvements. Read More

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April 2018
3 Reads

Upregulation of the aging related LMNA splice variant progerin in dilated cardiomyopathy.

PLoS One 2018 27;13(4):e0196739. Epub 2018 Apr 27.

Medical University Innsbruck, Department of Internal Medicine III, Cardiology and Angiology, Innsbruck, Tirol, Austria.

Background: Mutations in the LMNA gene are a common cause (6-8%) of dilated cardiomyopathy (DCM) leading to heart failure, a growing health care problem worldwide. The premature aging disease Hutchinson-Gilford syndrome (HGPS) is also caused by defined mutations in the LMNA gene resulting in activation of a cryptic splice donor site leading to a defective truncated prelamin A protein called progerin. Low levels of progerin are expressed in healthy individuals associated with ageing. Read More

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July 2018
2 Reads

MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies.

Aging Cell 2018 Apr 25:e12766. Epub 2018 Apr 25.

Aix Marseille Univ, INSERM, MMG, Marseille, France.

Hereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue-specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson-Gilford progeria syndrome (HGPS) and other progeroid syndromes. Read More

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April 2018
3 Reads

An overview of treatment strategies for Hutchinson-Gilford Progeria syndrome.

Nucleus 2018 Jan;9(1):246-257

a Aix Marseille Univ, INSERM, MMG - U1251 , Marseille , France.

Hutchinson-Gilford progeria syndrome (HGPS) is a sporadic, autosomal dominant disorder characterized by premature and accelerated aging symptoms leading to death at the mean age of 14.6 years usually due to cardiovascular complications. HGPS is caused by a de novo point mutation in the LMNA gene encoding the intermediate filament proteins lamins A and C which are structural components of the nuclear lamina. Read More

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January 2018
3 Reads

Mechanisms of vascular aging: What can we learn from Hutchinson-Gilford progeria syndrome?

Clin Investig Arterioscler 2018 May - Jun;30(3):120-132. Epub 2018 Mar 27.

CIBER de Enfermedades Cardiovasculares (CIBERCV), España; Institut de Recerca del Hospital de la Santa Creu i Sant Pau-Programa ICCC, IIB-Sant Pau, Barcelona, España. Electronic address:

Aging is the main risk factor for cardiovascular disease (CVD). The increased prevalence of CVD is partly due to the global increase in life expectancy. In this context, it is essential to identify the mechanisms by which aging induces CVD, with the ultimate aim of reducing its incidence. Read More

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October 2018
6 Reads

H, C and N backbone resonance assignment of the lamin C-terminal region specific to prelamin A.

Biomol NMR Assign 2018 Oct 26;12(2):225-229. Epub 2018 Mar 26.

Institut de Biologie Intégrative de la Cellule (I2BC), CEA, CNRS, Univ. Paris Sud, Université Paris-Saclay, Gif-sur-Yvette, France.

Lamins are the main components of the nucleoskeleton. They form a protein meshwork that underlies the inner nuclear membrane. Mutations in the LMNA gene coding for A-type lamins (lamins A and C) cause a large panel of human diseases, referred to as laminopathies. Read More

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October 2018
8 Reads

Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts.

Proc Natl Acad Sci U S A 2018 04 26;115(16):4206-4211. Epub 2018 Mar 26.

Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892;

encodes the A-type lamins that are part of the nuclear scaffold. Mutations in can cause a variety of disorders called laminopathies, including Hutchinson-Gilford progeria syndrome (HGPS), atypical Werner syndrome, and Emery-Dreifuss muscular dystrophy. Previous work has shown that treatment of HGPS cells with the mTOR inhibitor rapamycin or with the rapamycin analog everolimus corrects several of the phenotypes seen at the cellular level-at least in part by increasing autophagy and reducing the amount of progerin, the toxic form of lamin A that is overproduced in HGPS patients. Read More

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April 2018
8 Reads

Abnormal nuclear morphology is independent of longevity in a zmpste24-deficient fish model of Hutchinson-Gilford progeria syndrome (HGPS).

Comp Biochem Physiol C Toxicol Pharmacol 2018 Jul 19;209:54-62. Epub 2018 Mar 19.

Department of Preventive Medicine and Public Health, Kyorin University, School of Medicine, Tokyo 181-8611, Japan. Electronic address:

Lamin is an intermediate protein underlying the nuclear envelope and it plays a key role in maintaining the integrity of the nucleus. A defect in the processing of its precursor by a metalloprotease, ZMPSTE24, results in the accumulation of farnesylated prelamin in the nucleus and causes various diseases, including Hutchinson-Gilford progeria syndrome (HGPS). However, the role of lamin processing is unclear in fish species. Read More

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July 2018
12 Reads

Microbiome at sites of gingival recession in children with Hutchinson-Gilford progeria syndrome.

J Periodontol 2018 Jun;89(6):635-644

Department of Developmental Biology, Children's Hospital Boston, Boston, MA.

Background: Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder with significant oral and dental abnormalities. Clinical symptoms include various features of accelerated aging such as alopecia, loss of subcutaneous fat, bone abnormalities, and premature cardiovascular disease. In addition, children with HGPS have been observed to suffer from generalized gingival recession. Read More

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June 2018
9 Reads

Vascular Smooth Muscle-Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome.

Circulation 2018 Jul 28;138(3):266-282. Epub 2018 Feb 28.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (M.R.H., R.V.-B., P.G., M.J.A.-M., P.N., J.F.B., V.A.).

Background: Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). Patients who have HGPS exhibit ubiquitous progerin expression, accelerated aging and atherosclerosis, and die in their early teens, mainly of myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part, because of the lack of appropriate animal models. Read More

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July 2018
12 Reads

Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome.

Protein Cell 2018 Apr 23;9(4):333-350. Epub 2018 Feb 23.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Read More

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April 2018
7 Reads

A crucial role of ROCK for alleviation of senescence-associated phenotype.

Exp Gerontol 2018 06 21;106:8-15. Epub 2018 Feb 21.

Well Aging Research Center, DGIST, Daegu, Republic of Korea; The Future Life & Society Research Center, Chonnam National University, Gwangju, Republic of Korea. Electronic address:

In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. Read More

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June 2018
3 Reads

A Cell-Intrinsic Interferon-like Response Links Replication Stress to Cellular Aging Caused by Progerin.

Cell Rep 2018 Feb;22(8):2006-2015

Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA. Electronic address:

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by a truncated lamin A protein (progerin) that drives cellular and organismal decline. HGPS patient-derived fibroblasts accumulate genomic instability, but its underlying mechanisms and contribution to disease remain poorly understood. Here, we show that progerin-induced replication stress (RS) drives genomic instability by eliciting replication fork (RF) stalling and nuclease-mediated degradation. Read More

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February 2018
3 Reads
1 Citation
7.210 Impact Factor

Left Ventricular Diastolic Dysfunction in Hutchinson-Gilford Progeria Syndrome.

Authors:
Diane Fatkin

JAMA Cardiol 2018 Apr;3(4):334-335

Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.

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