690 results match your criteria Hutchinson-Gilford Progeria


Progerin accelerates atherosclerosis by inducing endoplasmic reticulum stress in vascular smooth muscle cells.

EMBO Mol Med 2019 Mar 12. Epub 2019 Mar 12.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by progerin, a mutant lamin A variant. HGPS patients display accelerated aging and die prematurely, typically from atherosclerosis complications. Recently, we demonstrated that progerin-driven vascular smooth muscle cell (VSMC) loss accelerates atherosclerosis leading to premature death in apolipoprotein E-deficient mice. Read More

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http://dx.doi.org/10.15252/emmm.201809736DOI Listing

Imbalanced nucleocytoskeletal connections create common polarity defects in progeria and physiological aging.

Proc Natl Acad Sci U S A 2019 Feb 11;116(9):3578-3583. Epub 2019 Feb 11.

Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032;

Studies of the accelerated aging disorder Hutchinson-Gilford progeria syndrome (HGPS) can potentially reveal cellular defects associated with physiological aging. HGPS results from expression and abnormal nuclear envelope association of a farnesylated, truncated variant of prelamin A called "progerin." We surveyed the diffusional mobilities of nuclear membrane proteins to identify proximal effects of progerin expression. Read More

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http://dx.doi.org/10.1073/pnas.1809683116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397528PMC
February 2019

The Cutting Edge: The Role of mTOR Signaling in Laminopathies.

Int J Mol Sci 2019 Feb 15;20(4). Epub 2019 Feb 15.

CNR National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna, 40136 Bologna, Italy.

The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase that regulates anabolic and catabolic processes, in response to environmental inputs. The existence of mTOR in numerous cell compartments explains its specific ability to sense stress, execute growth signals, and regulate autophagy. mTOR signaling deregulation is closely related to aging and age-related disorders, among which progeroid laminopathies represent genetically characterized clinical entities with well-defined phenotypes. Read More

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http://dx.doi.org/10.3390/ijms20040847DOI Listing
February 2019
2 Reads

Single-dose CRISPR-Cas9 therapy extends lifespan of mice with Hutchinson-Gilford progeria syndrome.

Nat Med 2019 Mar 18;25(3):419-422. Epub 2019 Feb 18.

Salk Institute for Biological Studies, La Jolla, CA, USA.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare lethal genetic disorder characterized by symptoms reminiscent of accelerated aging. The major underlying genetic cause is a substitution mutation in the gene coding for lamin A, causing the production of a toxic isoform called progerin. Here we show that reduction of lamin A/progerin by a single-dose systemic administration of adeno-associated virus-delivered CRISPR-Cas9 components suppresses HGPS in a mouse model. Read More

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http://dx.doi.org/10.1038/s41591-019-0343-4DOI Listing
March 2019
1 Read

Development of a CRISPR/Cas9-based therapy for Hutchinson-Gilford progeria syndrome.

Nat Med 2019 Mar 18;25(3):423-426. Epub 2019 Feb 18.

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.

CRISPR/Cas9-based therapies hold considerable promise for the treatment of genetic diseases. Among these, Hutchinson-Gilford progeria syndrome, caused by a point mutation in the LMNA gene, stands out as a potential candidate. Here, we explore the efficacy of a CRISPR/Cas9-based approach that reverts several alterations in Hutchinson-Gilford progeria syndrome cells and mice by introducing frameshift mutations in the LMNA gene. Read More

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http://dx.doi.org/10.1038/s41591-018-0338-6DOI Listing

Statins and Histone Deacetylase Inhibitors Affect Lamin A/C - Histone Deacetylase 2 Interaction in Human Cells.

Front Cell Dev Biol 2019 31;7. Epub 2019 Jan 31.

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

We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin A/C complexes in the DNA damage response. We further showed that lamin A/C-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin A/C interaction with HDAC2. Read More

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https://www.frontiersin.org/article/10.3389/fcell.2019.00006
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http://dx.doi.org/10.3389/fcell.2019.00006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365888PMC
January 2019
5 Reads

Neurogenesis and brain aging.

Rev Neurosci 2019 Feb 14. Epub 2019 Feb 14.

Research Center of Neurology, Moscow 125367, Russia.

Human aging affects the entire organism, but aging of the brain must undoubtedly be different from that of all other organs, as neurons are highly differentiated postmitotic cells, for the majority of which the lifespan in the postnatal period is equal to the lifespan of the entire organism. In this work, we examine the distinctive features of brain aging and neurogenesis during normal aging, pathological aging (Alzheimer's disease), and accelerated aging (Hutchinson-Gilford progeria syndrome and Werner syndrome). Read More

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http://dx.doi.org/10.1515/revneuro-2018-0084DOI Listing
February 2019
1 Read

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models.

Mol Cells 2019 Feb 1. Epub 2019 Feb 1.

Well Aging Research Center.

The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibition. However, it remains elusive whether this mechanism is also applicable to senescence amelioration in accelerated aging cells. Read More

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http://dx.doi.org/10.14348/molcells.2018.0352DOI Listing
February 2019
1 Read

Hutchinson-Gilford Progeria Syndrome-Current Status and Prospects for Gene Therapy Treatment.

Cells 2019 Jan 25;8(2). Epub 2019 Jan 25.

Laboratory of Nuclear Proteins, Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-383 Wroclaw, Poland.

Hutchinson-Gilford progeria syndrome (HGPS) is one of the most severe disorders among laminopathies-a heterogeneous group of genetic diseases with a molecular background based on mutations in the gene and genes coding for interacting proteins. HGPS is characterized by the presence of aging-associated symptoms, including lack of subcutaneous fat, alopecia, swollen veins, growth retardation, age spots, joint contractures, osteoporosis, cardiovascular pathology, and death due to heart attacks and strokes in childhood. codes for two major, alternatively spliced transcripts, give rise to lamin A and lamin C proteins. Read More

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http://dx.doi.org/10.3390/cells8020088DOI Listing
January 2019
2 Reads

A humanized yeast system to analyze cleavage of prelamin A by ZMPSTE24.

Methods 2019 Mar 6;157:47-55. Epub 2019 Jan 6.

Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address:

The nuclear lamins A, B, and C are intermediate filament proteins that form a nuclear scaffold adjacent to the inner nuclear membrane in higher eukaryotes, providing structural support for the nucleus. In the past two decades it has become evident that the final step in the biogenesis of the mature lamin A from its precursor prelamin A by the zinc metalloprotease ZMPSTE24 plays a critical role in human health. Defects in prelamin A processing by ZMPSTE24 result in premature aging disorders including Hutchinson Gilford Progeria Syndrome (HGPS) and related progeroid diseases. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10462023183012
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http://dx.doi.org/10.1016/j.ymeth.2019.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401292PMC
March 2019
3 Reads

Progerin expression induces a significant downregulation of transcription from human repetitive sequences in iPSC-derived dopaminergic neurons.

Authors:
Walter Arancio

Geroscience 2019 Jan 8. Epub 2019 Jan 8.

Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STeBiCeF), Viale delle Scienze, University of Palermo, Ed. 16, 90128, Palermo, PA, Italy.

Repetitive DNA sequences represent about half of the human genome. They have a central role in human biology, especially neurobiology, but are notoriously difficult to study. The purpose of this study was to quantify the transcription from repetitive sequences in a progerin-expressing cellular model of neuronal aging. Read More

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http://link.springer.com/10.1007/s11357-018-00050-2
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http://dx.doi.org/10.1007/s11357-018-00050-2DOI Listing
January 2019
1 Read

Induced Pluripotent Stem Cells to Study Mechanisms of Laminopathies: Focus on Epigenetics.

Front Cell Dev Biol 2018 20;6:172. Epub 2018 Dec 20.

Institute of Genetic and Biomedical Research, National Research Council of Italy, UOS of Milan, Milan, Italy.

Laminopathies are a group of rare degenerative disorders that manifest with a wide spectrum of clinical phenotypes, including both systemic multi-organ disorders, such as the Hutchinson-Gilford Progeria Syndrome (HGPS), and tissue-restricted diseases, such as Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy and lipodystrophies, often overlapping. Despite their clinical heterogeneity, which remains an open question, laminopathies are commonly caused by mutations in the LMNA gene, encoding the nuclear proteins Lamin A and C. These two proteins are main components of the nuclear lamina and are involved in several biological processes. Read More

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http://dx.doi.org/10.3389/fcell.2018.00172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306496PMC
December 2018
2 Reads

A nuclear lamina-chromatin-Ran GTPase axis modulates nuclear import and DNA damage signaling.

Aging Cell 2019 Feb 19;18(1):e12851. Epub 2018 Dec 19.

Center for Cell Signaling, University of Virginia, Charlottesville, Virginia.

The Ran GTPase regulates nuclear import and export by controlling the assembly state of transport complexes. This involves the direct action of RanGTP, which is generated in the nucleus by the chromatin-associated nucleotide exchange factor, RCC1. Ran interactions with RCC1 contribute to formation of a nuclear:cytoplasmic (N:C) Ran protein gradient in interphase cells. Read More

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http://dx.doi.org/10.1111/acel.12851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351833PMC
February 2019
2 Reads

New vascular insights into premature aging.

J Clin Invest 2019 Feb 18;129(2):492-493. Epub 2018 Dec 18.

Hutchinson-Gilford progeria syndrome (HGPS) is a fatal disease characterized by premature aging in which young children fail to thrive and adolescents die from myocardial infarction or stroke. The pathogenesis of HGPS is studied intensively because the mechanisms of premature aging may lead to a better understanding of normal aging. In this issue of the JCI, Osmanagic-Myers and colleagues identify the cellular mechanisms that lead to vascular abnormalities and death in children with HGPS. Read More

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https://www.jci.org/articles/view/125616
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http://dx.doi.org/10.1172/JCI125616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355212PMC
February 2019
2 Reads

Doubled lifespan and patient-like pathologies in progeria mice fed high-fat diet.

Aging Cell 2019 Feb 12;18(1):e12852. Epub 2018 Dec 12.

Edward A. Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiology of progeria mice early death, seemingly unrelated to the reported atherosclerosis contributing to HGPS patient mortality, and mice not recapitulating the severity of human disease. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.12852
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http://dx.doi.org/10.1111/acel.12852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351834PMC
February 2019
7 Reads

Telomere elongation through hTERT immortalization 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, England.

Immortalizing primary cells with human telomerase reverse transcriptase (hTERT) has been common practice to enable primary cells to be of extended use in the laboratory because they avoid replicative senescence. Studying exogenously expressed hTERT in cells also affords scientists models of early carcinogenesis and telomere behavior. Control and the premature ageing disease-Hutchinson-Gilford progeria syndrome (HGPS) primary dermal fibroblasts, with and without the classical G608G mutation have been immortalized with exogenous hTERT. Read More

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http://doi.wiley.com/10.1002/gcc.22711
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http://dx.doi.org/10.1002/gcc.22711DOI Listing
November 2018
83 Reads
4.041 Impact Factor

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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http://dx.doi.org/10.1007/s00439-018-1957-1DOI Listing
December 2018
7 Reads
4.824 Impact Factor

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

Neurobiol Aging 2019 Feb 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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http://dx.doi.org/10.1016/j.neurobiolaging.2018.10.015DOI Listing
February 2019
10 Reads

Endothelial progerin expression causes cardiovascular pathology through an impaired mechanoresponse.

J Clin Invest 2019 Feb 18;129(2):531-545. Epub 2018 Dec 18.

Max F. Perutz Laboratories (MFPL), Department of Medical Biochemistry, Medical University of Vienna and University of Vienna, Vienna Biocenter (VBC), Vienna, Austria.

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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http://www.jci.org/articles/view/121297
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http://dx.doi.org/10.1172/JCI121297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355303PMC
February 2019
10 Reads

HiPLA: High-throughput imaging proximity ligation assay.

Methods 2019 Mar 10;157:80-87. 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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https://linkinghub.elsevier.com/retrieve/pii/S10462023183011
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http://dx.doi.org/10.1016/j.ymeth.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401276PMC
March 2019
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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http://www.aging-us.com/article/101621/text
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http://dx.doi.org/10.18632/aging.101621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286842PMC
November 2018
15 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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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209416PMC
October 2018
1 Read

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

J Cell Biochem 2019 Apr 30;120(4):6277-6289. 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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http://doi.wiley.com/10.1002/jcb.27914
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http://dx.doi.org/10.1002/jcb.27914DOI Listing
April 2019
5 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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http://dx.doi.org/10.1038/s41598-018-33764-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193977PMC
October 2018
2 Reads

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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http://link.springer.com/10.1007/978-3-319-96445-4_5
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http://dx.doi.org/10.1007/978-3-319-96445-4_5DOI Listing
January 2018
2 Reads

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

Autophagy 2019 Mar 18;15(3):558-559. Epub 2018 Oct 18.

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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http://dx.doi.org/10.1080/15548627.2018.1533059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351129PMC
March 2019
12 Reads

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

Cell Tissue Res 2019 Mar 3;375(3):655-664. 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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http://dx.doi.org/10.1007/s00441-018-2930-yDOI Listing

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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http://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aa
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http://dx.doi.org/10.1126/scitranslmed.aat7163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166472PMC
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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http://dx.doi.org/10.1111/acel.12835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260922PMC
December 2018
5 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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https://linkinghub.elsevier.com/retrieve/pii/S22111247183122
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http://dx.doi.org/10.1016/j.celrep.2018.07.089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130051PMC
August 2018
14 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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http://dx.doi.org/10.18632/aging.101533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128420PMC
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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http://dx.doi.org/10.1111/acel.12824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156291PMC
October 2018
7 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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http://dx.doi.org/10.1007/s13238-018-0567-yDOI Listing
August 2018
14 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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http://dx.doi.org/10.18632/aging.101508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075434PMC
July 2018
5 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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http://cardiology.jamanetwork.com/article.aspx?doi=10.1001/j
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http://dx.doi.org/10.1001/jamacardio.2018.2103DOI Listing
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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http://dx.doi.org/10.1001/jamacardio.2018.2100DOI Listing
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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http://dx.doi.org/10.1016/j.mehy.2018.05.015DOI Listing
September 2018
37 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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http://dx.doi.org/10.1016/j.mehy.2018.06.029DOI Listing
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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040725PMC
June 2018
12 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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http://dx.doi.org/10.1155/2018/5028925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996419PMC
October 2018
3 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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http://dx.doi.org/10.1002/jbmr.3549DOI Listing
November 2018
2 Reads

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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http://dx.doi.org/10.1126/scisignal.aar5401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331045PMC
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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http://dx.doi.org/10.1080/19491034.2018.1476793DOI Listing
December 2018
6 Reads

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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http://dx.doi.org/10.1007/s11357-018-0030-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060207PMC
June 2018
2 Reads

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

Biogerontology 2018 12 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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http://link.springer.com/10.1007/s10522-018-9758-4
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http://dx.doi.org/10.1007/s10522-018-9758-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223735PMC
December 2018
13 Reads
3.290 Impact Factor

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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http://dx.doi.org/10.1038/s41598-018-27165-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002548PMC
June 2018
5 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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https://linkinghub.elsevier.com/retrieve/pii/S03069877173047
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http://dx.doi.org/10.1016/j.mehy.2018.04.018DOI Listing
July 2018
7 Reads

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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http://dx.doi.org/10.18632/oncotarget.25071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978267PMC
April 2018
3 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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http://dx.doi.org/10.1242/dmm.033670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078402PMC
July 2018
2 Reads