Nucleus 2018 Apr 5:1-27. Epub 2018 Apr 5.

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

Clin Investig Arterioscler 2018 Mar 27. 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

Biomol NMR Assign 2018 Mar 26. 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

Proc Natl Acad Sci U S A 2018 Apr 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

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

J Periodontol 2018 Feb 19. Epub 2018 Feb 19.

Department of Developmental Biology, Children's Hospital Boston, Boston, Massachusetts, USA.

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

Circulation 2018 Feb 28. Epub 2018 Feb 28.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain & Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain

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

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

Exp Gerontol 2018 Jun 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

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

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

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

JAMA Cardiol 2018 Apr;3(4):326-334

Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare disorder associated with premature death due to cardiovascular events during the second decade of life. However, because of its rarity (107 identified living patients), the natural history of cardiac disease remains uncharacterized. Therefore, meaningful cardiac end points for clinical trials have been difficult to establish. Read More

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

Aging Cell 2018 Apr 5;17(2). 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

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

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

J Clin Endocrinol Metab 2018 Mar;103(3):1005-1014

Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas.

Background: Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome (APS). Five of the 31 previously reported patients with APS harbored a recurrent de novo heterozygous LMNA p.T10I mutation. Read More

J Pediatr Adolesc Gynecol 2017 Dec 16. Epub 2017 Dec 16.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address:

Study Objective: This study identified the prevalence of menarche and coincident sexual characteristics in female adolescents with Hutchinson-Gilford Progeria Syndrome (HGPS).

Design: Data were examined to determine the prevalence of menarche in female adolescents older than 12 years; all were participants in clinical trials between 2007 and 2016.

Setting: Pediatric hospital in Boston, Massachusetts. Read More

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

Rev Neurosci 2018 Mar;29(3):233-240

Brain Research Department Research Center of Neurology, Moscow 125367, Russia.

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

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

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

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

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

Biochem Soc Trans 2017 12 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 a point mutation in exon 11 of the gene (c.1824C>T, p. Read More

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

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

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 the gene. 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

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

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

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

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

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

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

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

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

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

NPJ Aging Mech Dis 2016 10;2:16026. Epub 2016 Nov 10.

INSERM U861, I-STEM, AFM, Institute for Stem cell Therapy and Exploration of Monogenic Diseases, Corbeil Essonnes, France.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that causes systemic accelerated aging in children. This syndrome is due to a mutation in the gene that leads to the production of a truncated and toxic form of lamin A called progerin. Because the balance between the A-type lamins is controlled by the RNA-binding protein SRSF1, we have hypothesized that its inhibition may have therapeutic effects for HGPS. Read More

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

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 a point mutation in encoding A-type lamins. Progerin, a truncated and toxic prelamin A issued from aberrant splicing, accumulates in HGPS cells' nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. Read More

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

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

Mol Neurobiol 2018 May 28;55(5):4417-4427. 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

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

Aging (Albany NY) 2017 May;9(5):1453-1469

Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Bambino Gesu' Children's Research Hospital, IRCCS, Rome, 00146, Italy.

Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Read More

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

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

Metabolism 2017 06 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

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 the gene, resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. Read More

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