769 results match your criteria Hutchinson-Gilford Progeria


Progress and trends in the development of therapies for Hutchinson-Gilford progeria syndrome.

Aging Cell 2020 Jun 28:e13175. Epub 2020 Jun 28.

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.

Hutchinson-Gilford progeria syndrome (HGPS) is an autosomal-dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular complications. Till now clinical management of HGPS has largely relied on the treatment of manifestations and on the prevention of secondary complications, cure for the disease has not yet been established. Addressing this need cannot only benefit progeria patients but may also provide insights into intervention design for combating physiological aging. Read More

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http://dx.doi.org/10.1111/acel.13175DOI Listing

Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage.

Cell Metab 2020 Jun 17. Epub 2020 Jun 17.

Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. Electronic address:

Aging is a process of cellular and tissue dysfunction characterized by different hallmarks, including cellular senescence. However, there is proof that certain features of aging and senescence can be ameliorated. Here, we provide evidence that small extracellular vesicles (sEVs) isolated from primary fibroblasts of young human donors ameliorate certain biomarkers of senescence in cells derived from old and Hutchinson-Gilford progeria syndrome donors. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.004DOI Listing

Towards delineating the chain of events that cause premature senescence in the accelerated aging syndrome Hutchinson-Gilford progeria (HGPS).

Authors:
Oliver Dreesen

Biochem Soc Trans 2020 Jun;48(3):981-991

Cell Ageing Laboratory, Skin Research Institute of Singapore, 8A Biomedical Grove, #06-06 Immunos, 138648 Singapore.

The metazoan nucleus is equipped with a meshwork of intermediate filament proteins called the A- and B-type lamins. Lamins lie beneath the inner nuclear membrane and serve as a nexus to maintain the architectural integrity of the nucleus, chromatin organization, DNA repair and replication and to regulate nucleocytoplasmic transport. Perturbations or mutations in various components of the nuclear lamina result in a large spectrum of human diseases collectively called laminopathies. Read More

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http://dx.doi.org/10.1042/BST20190882DOI Listing

Lamin A/C Mechanotransduction in Laminopathies.

Cells 2020 May 24;9(5). Epub 2020 May 24.

Department of Chemistry, Materials and Chemical Engineering "G.Natta", Politecnico di Milano, 20133 Milano, Italy.

Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which are pathologies associated with mutations in lamins and lamin-associated proteins. These pathologies affect muscle, adipose, bone, nerve, and skin cells and range from muscular dystrophies to accelerated aging. Read More

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http://dx.doi.org/10.3390/cells9051306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291067PMC

Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome.

J R Soc Interface 2020 May 27;17(166):20200066. Epub 2020 May 27.

Department of Biomedical Engineering, Yale University, New Haven, CT, USA.

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS () using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Read More

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http://dx.doi.org/10.1098/rsif.2020.0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276555PMC

Epigenetic deregulation of lamina-associated domains in Hutchinson-Gilford progeria syndrome.

Genome Med 2020 May 25;12(1):46. Epub 2020 May 25.

Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.

Background: Hutchinson-Gilford progeria syndrome (HGPS) is a progeroid disease characterized by the early onset of age-related phenotypes including arthritis, loss of body fat and hair, and atherosclerosis. Cells from affected individuals express a mutant version of the nuclear envelope protein lamin A (termed progerin) and have previously been shown to exhibit prominent histone modification changes.

Methods: Here, we analyze the possibility that epigenetic deregulation of lamina-associated domains (LADs) is involved in the molecular pathology of HGPS. Read More

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http://dx.doi.org/10.1186/s13073-020-00749-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249329PMC

Lamin A involvement in ageing processes.

Ageing Res Rev 2020 May 21;62:101073. Epub 2020 May 21.

CNR Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza", Unit of Bologna, Bologna, Italy; IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address:

Lamin A, a main constituent of the nuclear lamina, is the major splicing product of the LMNA gene, which also encodes lamin C, lamin A delta 10 and lamin C2. Involvement of lamin A in the ageing process became clear after the discovery that a group of progeroid syndromes, currently referred to as progeroid laminopathies, are caused by mutations in LMNA gene. Progeroid laminopathies include Hutchinson-Gilford Progeria, Mandibuloacral Dysplasia, Atypical Progeria and atypical-Werner syndrome, disabling and life-threatening diseases with accelerated ageing, bone resorption, lipodystrophy, skin abnormalities and cardiovascular disorders. Read More

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http://dx.doi.org/10.1016/j.arr.2020.101073DOI Listing

Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells.

Cells 2020 May 12;9(5). Epub 2020 May 12.

Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition (ICAN), RHU CARMMA, Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Sorbonne Université, 75012 Paris, France.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder notably characterized by precocious and deadly atherosclerosis. Almost 90% of HGPS patients carry a LMNA p.G608G splice variant that leads to the expression of a permanently farnesylated abnormal form of prelamin-A, referred to as progerin. Read More

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http://dx.doi.org/10.3390/cells9051201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290406PMC

Evaluation of musculoskeletal phenotype of the G608G progeria mouse model with lonafarnib, pravastatin, and zoledronic acid as treatment groups.

Proc Natl Acad Sci U S A 2020 Jun 13;117(22):12029-12040. Epub 2020 May 13.

Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, MA 02215;

Hutchinson-Gilford progeria syndrome (HGPS) is a uniformly fatal condition that is especially prevalent in skin, cardiovascular, and musculoskeletal systems. A wide gap exists between our knowledge of the disease and a promising treatment or cure. The aim of this study was to first characterize the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and to determine the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. Read More

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http://dx.doi.org/10.1073/pnas.1906713117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275760PMC

Ultrasonic Characteristics of Cardiovascular Changes in Children with Hutchinson-Gilford Progeria Syndrome: A Comparative Study with Normal Children and Aging People.

Biomed Res Int 2020 13;2020:9631851. Epub 2020 Apr 13.

Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi Province, China.

Background: The cardiovascular characteristics of children with Hutchinson-Gilford progeria syndrome (HGPS) remain unclear. The present study is aimed at evaluating the cardiovascular changes with ultrasound examination in children with HGPS and compared these with those in normal children and older people.

Methods: Seven HGPS children, 21 age-matched healthy children, and 14 older healthy volunteers were evaluated by three-dimensional echocardiography (including strain analysis) and carotid elasticity examination with the echo-tracking technique. Read More

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http://dx.doi.org/10.1155/2020/9631851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180498PMC

Hutchinson-Gilford progeria syndrome and severe aortic stenosis: a new hope for treatment.

Ann Thorac Surg 2020 Apr 28. Epub 2020 Apr 28.

Department of Cardiac Surgery, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Hutchinson-Gilford progeria syndrome is an autosomal dominant, rare, fatal pediatric segmental premature aging disease. Cardiovascular and cerebrovascular diseases constitute the major cause of morbidity and mortality. Patients with HGPS and severe aortic valve stenosis have been described in literature and in all of them a strategy of conservative management has been followed. Read More

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http://dx.doi.org/10.1016/j.athoracsur.2020.03.067DOI Listing

PML2-mediated thread-like nuclear bodies mark late senescence in Hutchinson-Gilford progeria syndrome.

Aging Cell 2020 Jun 29;19(6):e13147. Epub 2020 Apr 29.

Shenzhen Key Laboratory for Systemic Aging and Intervention (SAI), National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China.

Progerin accumulation disrupts nuclear lamina integrity and causes nuclear structure abnormalities, leading to premature aging, that is, Hutchinson-Gilford progeria syndrome (HGPS). The roles of nuclear subcompartments, such as PML nuclear bodies (PML NBs), in HGPS pathogenesis, are unclear. Here, we show that classical dot-like PML NBs are reorganized into thread-like structures in HGPS patient fibroblasts and their presence is associated with late stage of senescence. Read More

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http://dx.doi.org/10.1111/acel.13147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294779PMC

Chromatin and Cytoskeletal Tethering Determine Nuclear Morphology in Progerin-Expressing Cells.

Biophys J 2020 May 14;118(9):2319-2332. Epub 2020 Apr 14.

Center for Complexity and Biosystems, Department of Environmental Science and Policy, University of Milan, Milano, Italy; CNR-Consiglio Nazionale delle Ricerche, Biophysics institute, Genova, Italy. Electronic address:

The nuclear morphology of eukaryotic cells is determined by the interplay between the lamina forming the nuclear skeleton, the chromatin inside the nucleus, and the coupling with the cytoskeleton. Nuclear alterations are often associated with pathological conditions as in Hutchinson-Gilford progeria syndrome, in which a mutation in the lamin A gene yields an altered form of the protein, named progerin, and an aberrant nuclear shape. Here, we introduce an inducible cellular model of Hutchinson-Gilford progeria syndrome in HeLa cells in which increased progerin expression leads to alterations in the coupling of the lamin shell with cytoskeletal or chromatin tethers as well as with polycomb group proteins. Read More

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http://dx.doi.org/10.1016/j.bpj.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203074PMC

Hutchinson-Gilford Progeria syndrome: Report of the first Togolese case.

Am J Med Genet A 2020 06 16;182(6):1316-1320. Epub 2020 Apr 16.

Département de Pédiatrie, CHU Sylvanus Olympio, Faculté des Sciences de la Santé, Université de Lomé, Lomé, Togo.

The aim of this article is to describe the first case of Hutchinson-Gilford Progeria Syndrome (HGPS) in Togo and review all Africans cases. Our patient was a 12.8-year-old Togolese boy followed in our unit till he was 15-year-old for HGPS. Read More

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http://dx.doi.org/10.1002/ajmg.a.61581DOI Listing

Accumulation of prelamin A induces premature aging through mTOR overactivation.

FASEB J 2020 Jun 13;34(6):7905-7914. Epub 2020 Apr 13.

Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, China.

Hutchinson-Gilford progeria syndrome (HGPS) arises when a truncated form of farnesylated prelamin A accumulates at the nuclear envelope, leading to misshapen nuclei. Previous studies of adult Zmpste24-deficient mice, a mouse model of progeria, have reported a metabolic response involving inhibition of the mTOR (mammalian target of rapamycin) kinase and activation of autophagy. However, exactly how mTOR or autophagy is involved in progeria remains unclear. Read More

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http://dx.doi.org/10.1096/fj.201903048RRDOI Listing
June 2020
5.043 Impact Factor

Overexpression of Progerin Results in Impaired Proliferation and Invasion of Non-Small Cell Lung Cancer Cells.

Onco Targets Ther 2020 30;13:2629-2642. Epub 2020 Mar 30.

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Dongguan, Guangdong, People's Republic of China.

Purpose: The accumulation of progerin (PG) in patients is responsible for the pathogenesis of Hutchinson-Gilford Progeria Syndrome (HGPS) because it triggers accelerated aging of cells. However, there are few studies on the effects of progerin on tumor cells. Lung cancer is one of the most common malignant cancers with high global morbidity and mortality rates; non-small cell lung cancer accounts for the majority of cases. Read More

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http://dx.doi.org/10.2147/OTT.S237016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127879PMC

Hutchinson-Gilford progeria syndrome: Rejuvenating old drugs to fight accelerated ageing.

Methods 2020 Apr 9. Epub 2020 Apr 9.

CECS, I-STEM AFM, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, 28 rue Henri Desbruères, 91100 Corbeil-Essonnes, France. Electronic address:

What if the next generation of successful treatments was hidden in the current pharmacopoeia? Identifying new indications for existing drugs, also called the drug repurposing or drug rediscovery process, is a highly efficient and low-cost strategy. First reported almost a century ago, drug repurposing has emerged as a valuable therapeutic option for diseases that do not have specific treatments and rare diseases, in particular. This review focuses on Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder that induces accelerated and precocious aging, for which drug repurposing has led to the discovery of several potential treatments over the past decade. Read More

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http://dx.doi.org/10.1016/j.ymeth.2020.04.005DOI Listing

Phosphorylated Lamin A/C in the Nuclear Interior Binds Active Enhancers Associated with Abnormal Transcription in Progeria.

Dev Cell 2020 Mar;52(6):699-713.e11

Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA; Department of Human Genetics, The University of Chicago, Chicago, IL 60637, USA; Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.

LMNA encodes nuclear Lamin A/C that tethers lamina-associated domains (LADs) to the nuclear periphery. Mutations in LMNA cause degenerative disorders including the premature aging disorder Hutchinson-Gilford progeria, but the mechanisms are unknown. We report that Ser22-phosphorylated (pS22) Lamin A/C was localized to the nuclear interior in human fibroblasts throughout the cell cycle. Read More

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http://dx.doi.org/10.1016/j.devcel.2020.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201903PMC

Nuclear protein export pathway in aging therapeutics.

Aging (Albany NY) 2020 Mar 19;12(6):4682-4684. Epub 2020 Mar 19.

Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico.

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http://dx.doi.org/10.18632/aging.102948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138584PMC

The JAK1/2 inhibitor ruxolitinib delays premature aging phenotypes.

Aging Cell 2020 Apr 20;19(4):e13122. Epub 2020 Mar 20.

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 caused by an LMNA mutation that results in the production of the abnormal progerin protein. Children with HGPS display phenotypes of premature aging and have an average lifespan of 13 years. We found earlier that the targeting of the transmembrane protein PLA2R1 overcomes senescence and improves phenotypes in a mouse model of progeria. Read More

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http://dx.doi.org/10.1111/acel.13122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189991PMC

Peroxisomal abnormalities and catalase deficiency in Hutchinson-Gilford Progeria Syndrome.

Aging (Albany NY) 2020 Mar 18;12(6):5195-5208. Epub 2020 Mar 18.

Department of Cell Biology and Molecular Genetics, College of Computer, Mathematical, and Natural Sciences, University of Maryland, College Park, MD 20742, USA.

Peroxisomes are small, membrane-enclosed eukaryotic organelles that house various enzymes with metabolic functions. One important feature in both Hutchinson-Gilford Progeria Syndrome (HGPS) and normal aging is the elevated levels of Reactive Oxygen Species (ROS), which are generated from metabolic pathways with the capacity to cause oxidative damage to macromolecules within the cells. Although peroxisomal bioreactions can generate free radicals as their byproducts, many metabolic enzymes within the peroxisomes play critical roles as ROS scavengers, in particular, catalase. Read More

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http://dx.doi.org/10.18632/aging.102941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138560PMC

Vascular Smooth Muscle Cell-Specific Progerin Expression Provokes Contractile Impairment in a Mouse Model of Hutchinson-Gilford Progeria Syndrome that Is Ameliorated by Nitrite Treatment.

Cells 2020 Mar 8;9(3). Epub 2020 Mar 8.

Laboratory of Molecular and Genetic Cardiovascular Pathophysiology, Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.

Cardiovascular disease (CVD) is the main cause of death worldwide, and aging is its leading risk factor. Aging is much accelerated in Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare genetic disorder provoked by the ubiquitous expression of a mutant protein called progerin. HGPS patients die in their teens, primarily due to cardiovascular complications. Read More

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http://dx.doi.org/10.3390/cells9030656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140649PMC

Anesthetic considerations in children with Hutchinson-Gilford progeria syndrome: A narrative review.

Paediatr Anaesth 2020 May 17;30(5):537-543. Epub 2020 Mar 17.

Section Anesthesiology and Algology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.

Background: Hutchinson-Gilford progeria syndrome is a rare disease in childhood that results in premature aging. The presence of multisystem derangements including skin, bone, and joint diseases and possibly a difficult airway makes the anesthetic management challenging. Because of the extremely low prevalence, experience is limited even for experienced pediatric anesthesiologists. Read More

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http://dx.doi.org/10.1111/pan.13847DOI Listing

Vascular endothelium-targeted gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model.

Sci Adv 2020 02 19;6(8):eaay5556. Epub 2020 Feb 19.

National Engineering Research Center for Biotechnology (Shenzhen), Carson International Cancer Center, Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China.

Vascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) mutation, called progerin. The ;TC mice with progerin expression induced by exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Read More

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http://dx.doi.org/10.1126/sciadv.aay5556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030934PMC
February 2020

Skeletal maturation and long-bone growth patterns of patients with progeria: a retrospective study.

Lancet Child Adolesc Health 2020 Apr 28;4(4):281-289. Epub 2020 Feb 28.

Department of Radiology, Boston Children's Hospital, Boston, MA, USA.

Background: Hutchinson-Gilford progeria syndrome (termed progeria in this Article) is a rare sporadic genetic disorder. One early clinical manifestation of progeria is abnormal skeletal growth, yet this growth has not been fully characterised. We aimed to characterise the skeletal maturation and long-bone growth patterns of patients with the clinical phenotype of progeria. Read More

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http://dx.doi.org/10.1016/S2352-4642(20)30023-7DOI Listing

Induced pluripotency and spontaneous reversal of cellular aging in supercentenarian donor cells.

Biochem Biophys Res Commun 2020 May 27;525(3):563-569. Epub 2020 Feb 27.

AgeX Therapeutics Inc., Alameda, CA, 94501, USA. Electronic address:

Supercentenarians (≥110-year-old, SC) are a uniquely informative population not only because they surpass centenarians in age, but because they appear to age more slowly with fewer incidences of chronic age-related disease than centenarians. We reprogramed donor B-lymphoblastoid cell lines (LCL) derived from a 114-year-old (SC), a 43-year-old healthy disease-free control (HDC) and an 8-year-old with a rapid aging disease (Hutchinson-Gilford progeria syndrome (HGPS)) and compared SC-iPSC to HDC-iPSC and HGPS-iPSCs. Reprogramming to pluripotency was confirmed by pluripotency marker expression and differentiation to 3 germ-layers. Read More

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http://dx.doi.org/10.1016/j.bbrc.2020.02.092DOI Listing

Nucleolar Organization and Functions in Health and Disease.

Cells 2020 Feb 25;9(3). Epub 2020 Feb 25.

Department of Biology, McGill University, Montreal H3A 1B1, Canada.

The nucleolus is a prominent, membraneless compartment found within the nucleus of eukaryotic cells. It forms around ribosomal RNA (rRNA) genes, where it coordinates the transcription, processing, and packaging of rRNA to produce ribosomal subunits. Recent efforts to characterize the biophysical properties of the nucleolus have transformed our understanding of the assembly and organization of this dynamic compartment. Read More

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http://dx.doi.org/10.3390/cells9030526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140423PMC
February 2020

Heterochromatin loss as a determinant of progerin-induced DNA damage in Hutchinson-Gilford Progeria.

Aging Cell 2020 Mar 22;19(3):e13108. Epub 2020 Feb 22.

Cell Ageing, Skin Research Institute Singapore, Singapore, Singapore.

Hutchinson-Gilford progeria is a premature aging syndrome caused by a truncated form of lamin A called progerin. Progerin expression results in a variety of cellular defects including heterochromatin loss, DNA damage, impaired proliferation and premature senescence. It remains unclear how these different progerin-induced phenotypes are temporally and mechanistically linked. Read More

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http://dx.doi.org/10.1111/acel.13108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059134PMC

Progeria: A Rare Genetic Syndrome.

Indian J Clin Biochem 2020 Jan 25;35(1):3-7. Epub 2019 Sep 25.

Department of Bioscience and Biotechnology, Banasthali University, Niwai, Tonk, Rajasthan 304022 India.

An uncommon deadly genetic situation symbolized by the presence of rapid maturation in infants is called as the Hutchinson-Gilford Progeria Syndrome. The term basically is meant as 'prematurely old' taken from the Greek meanings. The selective cause behind this syndrome is usually a mutation in a gene called LMNA. Read More

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http://dx.doi.org/10.1007/s12291-019-00849-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995454PMC
January 2020

Identification of hub genes, key pathways, and therapeutic agents in Hutchinson-Gilford Progeria syndrome using bioinformatics analysis.

Medicine (Baltimore) 2020 Feb;99(7):e19022

Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, China.

Background: Hutchinson-Gilford Progeria syndrome (HGPS) is a rare lethal premature and accelerated aging disease caused by mutations in the lamin A/C gene. Nevertheless, the mechanisms of cellular damage, senescence, and accelerated aging in HGPS are not fully understood. Therefore, we aimed to screen potential key genes, pathways, and therapeutic agents of HGPS by using bioinformatics methods in this study. Read More

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http://dx.doi.org/10.1097/MD.0000000000019022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035007PMC
February 2020

Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson-Gilford progeria syndrome.

Geroscience 2020 Apr 11;42(2):467-494. Epub 2020 Feb 11.

Faculty of Technology and Sciences, Lovely Professional University, Jalandhar - Delhi G.T. Road, Phagwara, Punjab, 144411, India.

Hutchinson-Gilford progeria syndrome (HGPS), commonly called progeria, is an extremely rare disorder that affects only one child per four million births. It is characterized by accelerated aging in affected individuals leading to premature death at an average age of 14.5 years due to cardiovascular complications. Read More

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http://dx.doi.org/10.1007/s11357-020-00167-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205988PMC

Metabolic Dysfunction in Hutchinson-Gilford Progeria Syndrome.

Cells 2020 Feb 8;9(2). Epub 2020 Feb 8.

Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, MO 63104, USA.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a segmental premature aging disease causing patient death by early teenage years from cardiovascular dysfunction. Although HGPS does not totally recapitulate normal aging, it does harbor many similarities to the normal aging process, with patients also developing cardiovascular disease, alopecia, bone and joint abnormalities, and adipose changes. It is unsurprising, then, that as physicians and scientists have searched for treatments for HGPS, they have targeted many pathways known to be involved in normal aging, including inflammation, DNA damage, epigenetic changes, and stem cell exhaustion. Read More

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http://dx.doi.org/10.3390/cells9020395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072593PMC
February 2020

Hutchinson-Gilford Progeria Syndrome with Bilateral Blephroptosis and Cataracts.

J Coll Physicians Surg Pak 2020 Feb;30(2):231-232

Centre of Biotechnology and Microbiology, University of Peshawar, Peshawar, Pakistan.

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http://dx.doi.org/10.29271/jcpsp.2020.02.231DOI Listing
February 2020

iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome.

Stem Cell Reports 2020 Feb 6;14(2):325-337. Epub 2020 Feb 6.

Department of Biomedical Engineering, Duke University, Durham, NC, USA. Electronic address:

Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we prepared tissue-engineered blood vessels (viTEBVs) using induced pluripotent stem cell-derived smooth muscle cells (viSMCs) and endothelial cells (viECs) from HGPS patients. Read More

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http://dx.doi.org/10.1016/j.stemcr.2020.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013250PMC
February 2020

Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells.

J Gerontol A Biol Sci Med Sci 2020 May;75(6):1073-1078

CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

Hutchinson-Gilford progeria syndrome (HGPS, or classical progeria) is a rare genetic disorder, characterized by premature aging, and caused by a de novo point mutation (C608G) within the lamin A/C gene (LMNA), producing an abnormal lamin A protein, termed progerin. Accumulation of progerin causes nuclear abnormalities and cell cycle arrest ultimately leading to cellular senescence. Autophagy impairment is a hallmark of cellular aging, and the rescue of this proteostasis mechanism delays aging progression in HGPS cells. Read More

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http://dx.doi.org/10.1093/gerona/glz280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243588PMC

G Protein-Coupled Receptor Systems and Their Role in Cellular Senescence.

Comput Struct Biotechnol J 2019 23;17:1265-1277. Epub 2019 Aug 23.

Receptor Biology Lab, University of Antwerp, 2610 Antwerp, Belgium.

Aging is a complex biological process that is inevitable for nearly all organisms. Aging is the strongest risk factor for development of multiple neurodegenerative disorders, cancer and cardiovascular disorders. Age-related disease conditions are mainly caused by the progressive degradation of the integrity of communication systems within and between organs. Read More

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http://dx.doi.org/10.1016/j.csbj.2019.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944711PMC

Calcitriol Prevents RAD51 Loss and cGAS-STING-IFN Response Triggered by Progerin.

Proteomics 2020 03 30;20(5-6):e1800406. Epub 2019 Dec 30.

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

Hutchinson Gilford progeria syndrome (HGPS) is a devastating accelerated aging disease caused by LMNA gene mutation. The truncated lamin A protein produced "progerin" has a dominant toxic effect in cells, causing disruption of nuclear architecture and chromatin structure, genomic instability, gene expression changes, oxidative stress, and premature senescence. It was previously shown that progerin-induced genomic instability involves replication stress (RS), characterized by replication fork stalling and nuclease-mediated degradation of stalled forks. Read More

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http://dx.doi.org/10.1002/pmic.201800406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117971PMC

Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis.

Aging Cell 2020 02 12;19(2):e13090. Epub 2019 Dec 12.

Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Taiwan.

Mutations in lamin A (LMNA) are responsible for a variety of human dystrophic and metabolic diseases. Here, we created a mouse model in which progerin, the lamin A mutant protein that causes Hutchinson-Gilford progeria syndrome (HGPS), can be inducibly overexpressed. Muscle-specific overexpression of progerin was sufficient to induce muscular dystrophy and alter whole-body energy expenditure, leading to premature death. Read More

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http://dx.doi.org/10.1111/acel.13090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996945PMC
February 2020

Databases to Efficiently Manage Medium Sized, Low Velocity, Multidimensional Data in Tissue Engineering.

J Vis Exp 2019 11 22(153). Epub 2019 Nov 22.

Department of Biomedical Engineering, University of California, Irvine; The Edwards Lifesciences Center for Advanced Cardiovascular Technology, University of California, Irvine; Department of Chemical and Biomolecular Engineering, University of California, Irvine; Center for Complex Biological Systems, University of California, Irvine; The NSF-Simons Center for Multiscale Cell Fate Research (CMCF), University of California, Irvine;

Science relies on increasingly complex data sets for progress, but common data management methods such as spreadsheet programs are inadequate for the growing scale and complexity of this information. While database management systems have the potential to rectify these issues, they are not commonly utilized outside of business and informatics fields. Yet, many research labs already generate "medium sized", low velocity, multi-dimensional data that could greatly benefit from implementing similar systems. Read More

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http://dx.doi.org/10.3791/60038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156791PMC
November 2019

Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models.

Exp Gerontol 2020 Feb 30;130:110784. Epub 2019 Nov 30.

CNR - Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza"- Unit of Bologna, Bologna, Italy; IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address:

The transgenic Lmna progeric mouse represents an outstanding animal model for studying the human Hutchinson-Gilford Progeria Syndrome (HGPS) caused by a mutation in the LMNA gene, coding for the nuclear envelope protein Lamin A/C, and, as an important, more general scope, for studying the complex process governing physiological aging in humans. Here we give a comprehensive description of the peculiarities related to the breeding of Lmna mice over a prolonged period of time, and of many features observed in a large colony for a 2-years period. We describe the breeding and housing conditions underlining the possible interference of the genetic background on the phenotype expression. Read More

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http://dx.doi.org/10.1016/j.exger.2019.110784DOI Listing
February 2020

Obstructive sleep apnea in Hutchinson-Gilford progeria.

Sleep Med 2020 02 8;66:21-23. Epub 2019 Aug 8.

KU Leuven, Department of Chronic Disease, Metabolism and Ageing, Leuven, Belgium; University Hospital Leuven, Leuven University Centre for Sleep and Wake Disorders and Department of Pulmonology, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.sleep.2019.08.001DOI Listing
February 2020

Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson-Gilford Progeria Syndrome.

Nat Commun 2019 11 18;10(1):4990. Epub 2019 Nov 18.

IFOM Foundation-FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139, Milan, Italy.

Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Read More

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http://dx.doi.org/10.1038/s41467-019-13018-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861280PMC
November 2019

Premature aging syndromes: From patients to mechanism.

J Dermatol Sci 2019 Nov 22;96(2):58-65. Epub 2019 Oct 22.

Cell Aging Laboratory, Skin Research Institute of Singapore, 8A Biomedical Grove, #06-06 Immunos, 138648 Singapore; Nanyang Technological University, Singapore. Electronic address:

Aging is an inevitable consequence of human life resulting in a gradual deterioration of cell, tissue and organismal function and an increased risk to develop chronic ailments. Premature aging syndromes, also known as progeroid syndromes, recapitulate many clinical features of normal aging and offer a unique opportunity to elucidate fundamental mechanisms that contribute to human aging. Progeroid syndromes can be broadly classified into those caused by perturbations of the nuclear lamina, a meshwork of proteins located underneath the inner nuclear membrane (laminopathies); and a second group that is caused by mutations that directly impair DNA replication and repair. Read More

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http://dx.doi.org/10.1016/j.jdermsci.2019.10.003DOI Listing
November 2019

Lysophosphatidic acid receptor LPA prevents oxidative stress and cellular senescence in Hutchinson-Gilford progeria syndrome.

Aging Cell 2020 01 12;19(1):e13064. Epub 2019 Nov 12.

Department of Life Science, National Taiwan University, Taipei, Taiwan.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin, resulting in premature aging. HGPS cells show morphological abnormalities of the nuclear membrane, reduced cell proliferation rates, accumulation of reactive oxygen species (ROS), and expression of senescence markers. Lysophosphatidic acid (LPA) is a growth factor-like lipid mediator that regulates various physiological functions via activating multiple LPA G protein-coupled receptors. Read More

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http://dx.doi.org/10.1111/acel.13064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974717PMC
January 2020
6.340 Impact Factor

ATP-based therapy prevents vascular calcification and extends longevity in a mouse model of Hutchinson-Gilford progeria syndrome.

Proc Natl Acad Sci U S A 2019 11 5;116(47):23698-23704. Epub 2019 Nov 5.

Fundación Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain

Pyrophosphate deficiency may explain the excessive vascular calcification found in children with Hutchinson-Gilford progeria syndrome (HGPS) and in a mouse model of this disease. The present study found that hydrolysis products of ATP resulted in a <9% yield of pyrophosphate in wild-type blood and aortas, showing that eNTPD activity (ATP → phosphate) was greater than eNPP activity (ATP → pyrophosphate). Moreover, pyrophosphate synthesis from ATP was reduced and pyrophosphate hydrolysis (via TNAP; pyrophosphate → phosphate) was increased in both aortas and blood obtained from mice with HGPS. Read More

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http://dx.doi.org/10.1073/pnas.1910972116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876227PMC
November 2019

Lamin A/C promotes DNA base excision repair.

Nucleic Acids Res 2019 12;47(22):11709-11728

Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, DK-2200 Copenhagen, Denmark.

The A-type lamins (lamin A/C), encoded by the LMNA gene, are important structural components of the nuclear lamina. LMNA mutations lead to degenerative disorders known as laminopathies, including the premature aging disease Hutchinson-Gilford progeria syndrome. In addition, altered lamin A/C expression is found in various cancers. Read More

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http://dx.doi.org/10.1093/nar/gkz912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145687PMC
December 2019
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Inhibition of JAK-STAT Signaling with Baricitinib Reduces Inflammation and Improves Cellular Homeostasis in Progeria Cells.

Cells 2019 10 18;8(10). Epub 2019 Oct 18.

Epigenetics of Aging, Department of Dermatology and Allergy, TUM school of Medicine, Technical University of Munich (TUM), 85748 Garching, Germany.

Hutchinson-Gilford progeria syndrome (HGPS), 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 gene. Nearly 90% of HGPS cases carry the G608G mutation within exon 11 that generates a truncated prelamin A protein "progerin". Read More

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http://dx.doi.org/10.3390/cells8101276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829898PMC
October 2019
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Age-related neurodegenerative diseases.

J Cell Physiol 2020 Apr 25;235(4):3131-3141. Epub 2019 Sep 25.

Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

Converging evidence indicates the dysregulation of unique cytosolic compartments called stress granules (SGs) might facilitate the accumulation of toxic protein aggregates that underlie many age-related neurodegenerative pathologies (ANPs). SG dynamics are particularly susceptible to the cellular conditions that are commonly induced by aging, including the elevation in reactive oxygen species and increased concentration of aggregate-prone proteins. In turn, the persistent formation of these compartments is hypothesized to serve as a seed for subsequent protein aggregation. Read More

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http://dx.doi.org/10.1002/jcp.29248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029396PMC

Recent Advances on the Structure and Function of RNA Acetyltransferase Kre33/NAT10.

Cells 2019 09 5;8(9). Epub 2019 Sep 5.

Département des Sciences Biologiques and Centre d'Excellence en Recherche sur les Maladies Orphelines-Fondation Courtois (CERMO-FC), Université du Québec à Montréal, Montréal, QC H3C 3P8, Canada.

Ribosome biogenesis is one of the most energy demanding processes in the cell. In eukaryotes, the main steps of this process occur in the nucleolus and include pre-ribosomal RNA (pre-rRNA) processing, post-transcriptional modifications, and assembly of many non-ribosomal factors and ribosomal proteins in order to form mature and functional ribosomes. In yeast and humans, the nucleolar RNA acetyltransferase Kre33/NAT10 participates in different maturation events, such as acetylation and processing of 18S rRNA, and assembly of the 40S ribosomal subunit. Read More

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http://dx.doi.org/10.3390/cells8091035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770127PMC
September 2019

Hereditary Syndromes with Signs of Premature Aging.

Dtsch Arztebl Int 2019 07;116(29-30):489-496

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg.

Background: Segmental progeroid syndromes (SPS) are rare hereditary diseases in which the affected individuals show signs of premature aging in more than one organ or type of tissue. We review the clinical and genetic features of some of these syndromes and discuss the extent to which their study affords a complementary opportunity to study aging processes in general.

Methods: This review is based on publications retrieved by a selective search in PubMed. Read More

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http://dx.doi.org/10.3238/arztebl.2019.0489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726857PMC
July 2019
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