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    623 results match your criteria Hutchinson-Gilford Progeria

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    p53 isoforms regulate premature aging in human cells.
    Oncogene 2018 Feb 12. Epub 2018 Feb 12.
    Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA.
    Cellular senescence is a hallmark of normal aging and aging-related syndromes, including the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder caused by a single mutation in the LMNA gene that results in the constitutive expression of a truncated splicing mutant of lamin A known as progerin. Progerin accumulation leads to increased cellular stresses including unrepaired DNA damage, activation of the p53 signaling pathway and accelerated senescence. We previously established that the p53 isoforms ∆133p53 and p53β regulate senescence in normal human cells. Read More

    Smurf2 regulates stability and the autophagic-lysosomal turnover of lamin A and its disease-associated form progerin.
    Aging Cell 2018 Feb 5. Epub 2018 Feb 5.
    Laboratory of Molecular and Cellular Cancer Biology, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
    A-lamins, encoded by the LMNA gene, are major structural components of the nuclear lamina coordinating essential cellular processes. Mutations in the LMNA gene and/or alterations in its expression levels have been linked to a distinct subset of human disorders, collectively known as laminopathies, and to cancer. Mechanisms regulating A-lamins are mostly obscure. Read More

    Progeria: case report and new drugs perspectives.
    J Eur Acad Dermatol Venereol 2018 Jan 29. Epub 2018 Jan 29.
    HUGV - Hospital Universitário Getúlio Vargas (Rua Apurina Dermatology Department, 04 - Praca 14 de Janeiro, Manaus, AM69020-170, Brazil.
    Hutchinson-Gilford progeria syndrome (HGPS) is one of the rarest human diseases, an autosomal dominant premature aging disorder. Its incidence is 1-4 per 8 million newborns. There are aging-associated symptoms, including lack of subcutaneous fat, hair loss, joint contractures, progressive cardiovascular disease resembling atherosclerosis, and death due to heart attacks and strokes in childhood. Read More

    Nucleoplasmic lamins define growth-regulating functions of lamina-associated polypeptide 2α in progeria cells.
    J Cell Sci 2018 Feb 8;131(3). Epub 2018 Feb 8.
    Max F. Perutz Laboratories (MFPL), Center of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, A-1030 Vienna, Austria
    A-type lamins are components of the peripheral nuclear lamina but also localize in the nuclear interior in a complex with lamina-associated polypeptide (LAP) 2α. Loss of LAP2α and nucleoplasmic lamins in wild-type cells increases cell proliferation, but in cells expressing progerin (a mutant lamin A that causes Hutchinson-Gilford progeria syndrome), low LAP2α levels result in proliferation defects. Here, the aim was to understand the molecular mechanism governing how relative levels of LAP2α, progerin and nucleoplasmic lamins affect cell proliferation. Read More

    Survey of plasma proteins in children with progeria pre-therapy and on-therapy with lonafarnib.
    Pediatr Res 2018 Jan 17. Epub 2018 Jan 17.
    The Vascular Biology Program and The Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
    Background: Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare, fatal, segmental premature aging syndrome caused by the aberrant lamin A protein, progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease.

    Study Design: We performed a prospective longitudinal survey of plasma proteins in 24 children with HGPS (an estimated 10% of the world's population at the time) at baseline and on lonafarnib therapy, compared to age and gender-matched controls using a multi-analyte, microsphere-based immune-fluorescent assay. Read More

    A Novel Generalized Lipodystrophy-associated Progeroid Syndrome due to recurrent heterozygous LMNA p.T10I Mutation.
    J Clin Endocrinol Metab 2017 Dec 15. Epub 2017 Dec 15.
    Center for Human Nutrition, Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.
    Background: Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders including Hutchinson-Gilford progeria syndrome (HGPS), mandibuloacral dysplasia, and atypical progeroid syndrome (APS). Five of the 31 previously reported APS patients harbored a recurrent de novo heterozygous LMNA p.T10I mutation. Read More

    DNA replication timing alterations identify common markers between distinct progeroid diseases.
    Proc Natl Acad Sci U S A 2017 Dec 1;114(51):E10972-E10980. Epub 2017 Dec 1.
    Department of Biological Science, Florida State University, Tallahassee, FL 32306;
    Progeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Different causal mutations have been identified, but no molecular alterations have been identified that are in common to these diseases. DNA replication timing (RT) is a robust cell type-specific epigenetic feature highly conserved in the same cell types from different individuals but altered in disease. Read More

    Accelerated aging and aging process in the brain.
    Rev Neurosci 2017 Nov 18. Epub 2017 Nov 18.
    .
    One of the approaches to the research of the problem of aging is the study of genetic pathologies leading to accelerated aging, such as the Hutchinson-Gilford progeria syndrome, Werner syndrome, and Down syndrome. Probably, this approach can be used in an attempt to understand the neuronal mechanisms underlying normal and pathological brain aging. The analysis of the current state of scientific knowledge about these pathologies shows that in the Hutchinson-Gilford progeria and Werner syndrome, the rate of brain aging is significantly lower than the rate of whole body aging, whereas in Down syndrome, the brain ages faster than other organs due to amyloid-beta accumulation and chronic oxidative stress in the brain tissue. Read More

    Are There Different Kinds of Aging?
    Curr Aging Sci 2017 Nov 16. Epub 2017 Nov 16.
    University Politehnica Bucharest. Romania.
    A critical analysis of the accelerated aging syndromes may explain what aging is, but also why some tissues and organs age at accelerated rates in comparison with aging rates of other tissues. Syndromes of accelerated aging are caused by mutations affecting the integrity of the genetic material. Among them, the most studied is Werner's syndrome, "adult progeria", caused by a recessive autosomal mutation with a frequency of 1 in 10 millions, which affects a helicase involved in DNA repair. Read More

    Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations.
    PLoS One 2017 17;12(11):e0188256. Epub 2017 Nov 17.
    Departments of Biomedical Engineering, University of California, Irvine, CA, United States of America.
    Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. Read More

    Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins.
    Mol Biol Cell 2018 Jan 15;29(2):220-233. Epub 2017 Nov 15.
    Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
    Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed "blebs" are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. Read More

    Radiological Diagnosis of a Rare Premature Aging Genetic Disorder: Progeria (Hutchinson-Gilford Syndrome).
    Case Rep Radiol 2017 12;2017:1305360. Epub 2017 Sep 12.
    Saveetha Medical College and Hospital, Saveetha Nagar, Thandalam, Chennai, Tamil Nadu 602105, India.
    Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare disease with a combination of short stature, bone abnormalities, premature ageing, and skin changes. Though the physical appearance of these patients is characteristic, there is little emphasis on the characteristic radiological features. In this paper, we report a 16-year-old boy with clinical and radiological features of this rare genetic disorder. Read More

    Emerging candidate treatment strategies for Hutchinson-Gilford progeria syndrome.
    Biochem Soc Trans 2017 Dec 10;45(6):1279-1293. Epub 2017 Nov 10.
    Department of Biosciences and Nutrition, Center for Innovative Medicine, Karolinska Institutet, Huddinge, Sweden
    Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million individuals. HGPS is usually caused by apoint mutation in exon 11 of thegene (c.1824C>T, p. Read More

    The Potential of iPSCs for the Treatment of Premature Aging Disorders.
    Int J Mol Sci 2017 Nov 7;18(11). Epub 2017 Nov 7.
    Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Diseases, Children's Research Hospital Bambino Gesù, IRCCS, 00146 Rome, Italy.
    Premature aging disorders including Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome, are a group of rare monogenic diseases leading to reduced lifespan of the patients. Importantly, these disorders mimic several features of physiological aging. Despite the interest on the study of these diseases, the underlying biological mechanisms remain unknown and no treatment is available. Read More

    Protein sequestration at the nuclear periphery as a potential regulatory mechanism in premature aging.
    J Cell Biol 2018 Jan 19;217(1):21-37. Epub 2017 Oct 19.
    National Cancer Institute, National Institutes of Health, Bethesda, MD
    Despite the extensive description of numerous molecular changes associated with aging, insights into the driver mechanisms of this fundamental biological process are limited. Based on observations in the premature aging syndrome Hutchinson-Gilford progeria, we explore the possibility that protein regulation at the inner nuclear membrane and the nuclear lamina contributes to the aging process. In support, sequestration of nucleoplasmic proteins to the periphery impacts cell stemness, the response to cytotoxicity, proliferation, changes in chromatin state, and telomere stability. Read More

    Intermittent treatment with farnesyltransferase inhibitor and sulforaphane improves cellular homeostasis in Hutchinson-Gilford progeria fibroblasts.
    Oncotarget 2017 Sep 18;8(39):64809-64826. Epub 2017 Jul 18.
    Department of Dermatology, Epigenetics of Aging, TUM School of Medicine, Technische Universität München, Garching-Munich, Germany.
    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic condition associated with mutations in thegene. This disease recapitulates some aspects of normal aging, such as hair loss, thin skin, joint stiffness, and atherosclerosis. The latter leads to heart attack or stroke that causes death at an average age of 14. Read More

    Aging in the Cardiovascular System: Lessons from Hutchinson-Gilford Progeria Syndrome.
    Annu Rev Physiol 2018 02 20;80:27-48. Epub 2017 Sep 20.
    Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain; email:
    Aging, the main risk factor for cardiovascular disease (CVD), is becoming progressively more prevalent in our societies. A better understanding of how aging promotes CVD is therefore urgently needed to develop new strategies to reduce disease burden. Atherosclerosis and heart failure contribute significantly to age-associated CVD-related morbimortality. Read More

    On the discovery of new potent human farnesyltransferase inhibitors: emerging pyroglutamic derivatives.
    Org Biomol Chem 2017 Oct;15(38):8110-8118
    Inserm U995, LIRIC, Université de Lille, CHRU de Lille, Faculté de médecine - Pôle recherche, Place Verdun, F-59045 Lille Cedex, France.
    In the current context of lack of emergence of innovative human farnesyltransferase inhibitors families, and given all new therapeutic perspectives that open up for such molecules in rare diseases (e.g. Hutchinson-Gilford progeria syndrome), and in delta hepatitis, cardiovascular or neuroinflammatory diseases, we have just discovered a new series of powerful inhibitors. Read More

    The clinical characteristics of Asian patients with classical-type Hutchinson-Gilford progeria syndrome.
    J Hum Genet 2017 Dec 7;62(12):1031-1035. Epub 2017 Sep 7.
    Department of Pediatrics, Faculty of Medicine, Oita University, Yufu, Japan.
    Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder that shows a characteristic progeria phenotype. We conducted a questionnaire survey of 1173 tertiary hospitals in Japan and reviewed the academic reports, to identify the characteristics of Asian patients with classical HGPS. As a result, four Japanese patients were identified; this was estimated to account for approximately two-third of the prevalence in Japan. Read More

    Identification of novel RNA isoforms of LMNA.
    Nucleus 2017 09 31;8(5):573-582. Epub 2017 Aug 31.
    a National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
    The nuclear lamina is a proteinaceous meshwork situated underneath the inner nuclear membrane and is composed of nuclear lamin proteins, which are type-V intermediate filaments. The LMNA gene gives rise to lamin A and lamin C through alternative splicing. Mutations in LMNA cause multiple diseases known as laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disorder caused by a point mutation that activates a cryptic 5' splice site in exon 11, resulting in a 150 bp deletion in the LMNA mRNA and the production of the dominant lamin A isoform progerin. Read More

    Nucleolar expansion and elevated protein translation in premature aging.
    Nat Commun 2017 08 30;8(1):328. Epub 2017 Aug 30.
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA.
    Premature aging disorders provide an opportunity to study the mechanisms that drive aging. In Hutchinson-Gilford progeria syndrome (HGPS), a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We sought to investigate protein homeostasis in this disease. Read More

    A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells.
    Sci Rep 2017 Aug 15;7(1):8168. Epub 2017 Aug 15.
    Department of Biomedical Engineering at Duke University, Durham, NC, 27708, United States.
    Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Read More

    Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.
    Nat Rev Mol Cell Biol 2017 Oct 9;18(10):595-609. Epub 2017 Aug 9.
    National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Read More

    Ophthalmologic Features of Progeria.
    Am J Ophthalmol 2017 Oct 27;182:126-132. Epub 2017 Jul 27.
    Department of Anesthesia, Boston Children's Hospital - Harvard Medical School, Boston, Massachusetts; Department of Pediatrics, Hasbro Children's Hospital - Warren Alpert Medical School of Brown University, Providence, Rhode Island.
    Purpose: To establish the natural history of ophthalmic characteristics in Progeria patients and to determine incidence of ocular manifestations.

    Design: Retrospective case series of patients with Progeria who were seen between 2007 and 2016.

    Methods: Setting: Tertiary-care academic center. Read More

    Redox imbalance in a model of rat mimicking Hutchinson-Gilford progeria syndrome.
    Biochem Biophys Res Commun 2017 09 17;491(2):361-367. Epub 2017 Jul 17.
    Department of Biochemistry, University of Allahabad, Allahabad 211002, India. Electronic address:
    Although several etiological factors contribute to the complexity of the aging process, the ultimate component of macromolecular damage and consequent cell death involves the altered redox balance inclined towards increased ROS production and/or decreased antioxidant protection. Given that, the chronic dihydrotachysterol (DHT) intoxication in rats induce Hutchinson Gilford progeria like syndrome, the present study provides the evidence for altered redox balance as evidenced by alteration in parameters of oxidative stress in blood plasma and erythrocytes including MDA, GSH, FRAP AOPP PMRS, AGEs, AChE and osmotic fragility which substantiate the suitability of the model for aging studies. Read More

    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 thegene 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 10 28;229:77-83. 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 Sep;9(9):1294-1313
    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 apoint mutation inencoding 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 prolongedculture 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 Jul 30;8(4):433-446. 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 09 17;31(9):3882-3893. 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 thegene, 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 Oct 6;25(3-4):227-239. 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 05 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 Oct 3;26(10):889-895. Epub 2017 May 3.
    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 03 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 thegene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. Read More

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