The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin
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{"title"=>"The mutant form of Lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin", "type"=>"journal", "authors"=>[{"first_name"=>"Dayle", "last_name"=>"McClintock", "scopus_author_id"=>"8901754000"}, {"first_name"=>"Desiree", "last_name"=>"Ratner", "scopus_author_id"=>"7006012037"}, {"first_name"=>"Meepa", "last_name"=>"Lokuge", "scopus_author_id"=>"24329864600"}, {"first_name"=>"David M.", "last_name"=>"Owens", "scopus_author_id"=>"56345656700"}, {"first_name"=>"Leslie B.", "last_name"=>"Gordon", "scopus_author_id"=>"35314281700"}, {"first_name"=>"Francis S.", "last_name"=>"Collins", "scopus_author_id"=>"55574146000"}, {"first_name"=>"Karima", "last_name"=>"Djabali", "scopus_author_id"=>"6701702305"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"351722482", "sgr"=>"41649101975", "issn"=>"19326203", "pmid"=>"18060063", "scopus"=>"2-s2.0-41649101975", "doi"=>"10.1371/journal.pone.0001269", "isbn"=>"1932-6203 (Electronic)"}, "id"=>"f735a60b-65c1-3ede-8839-1a935737ba8f", "abstract"=>"Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by accelerated aging and early death, frequently from stroke or coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT) mutation within exon 11 of LMNA, activating a splice donor site that results in production of a dominant negative form of lamin A protein, denoted progerin. Screening 150 skin biopsies from unaffected individuals (newborn to 97 years) showed that a similar splicing event occurs in vivo at a low level in the skin at all ages. While progerin mRNA remains low, the protein accumulates in the skin with age in a subset of dermal fibroblasts and in a few terminally differentiated keratinocytes. Progerin-positive fibroblasts localize near the basement membrane and in the papillary dermis of young adult skin; however, their numbers increase and their distribution reaches the deep reticular dermis in elderly skin. Our findings demonstrate that progerin expression is a biomarker of normal cellular aging and may potentially be linked to terminal differentiation and senescence in elderly individuals.", "link"=>"http://www.mendeley.com/research/mutant-form-lamin-causes-hutchinsongilford-progeria-biomarker-cellular-aging-human-skin", "reader_count"=>139, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>29, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>34, "Student > Postgraduate"=>4, "Student > Master"=>14, "Other"=>7, "Student > Bachelor"=>33, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>6, "Researcher"=>29, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>34, "Student > Postgraduate"=>4, "Student > Master"=>14, "Other"=>7, "Student > Bachelor"=>33, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Agricultural and Biological Sciences"=>80, "Business, Management and Accounting"=>1, "Chemistry"=>4, "Computer Science"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>28, "Mathematics"=>1, "Medicine and Dentistry"=>12, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Psychology"=>2, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>80}, "Computer Science"=>{"Computer Science"=>2}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>28}}, "reader_count_by_country"=>{"Canada"=>1, "United States"=>3, "Japan"=>3, "Finland"=>1, "Egypt"=>1, "France"=>2, "Portugal"=>1, "India"=>1}, "group_count"=>6}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/940815"], "description"=>"<p>A, HGPS skin sections immunostained with anti-progerin (prog), anti-lamin A (LMNA) antibody, or anti-α smooth muscle actin antibody (αSMA) and counterstained with a DNA stain (dapi). Morphologic entities are indicated: epidermis (ep), dermis (de), sweat glands (SG), capillary (c), arrector pili muscle (a), and hair follicle (h). B, Newborn foreskin sections immunolabelled with anti-progerin or anti-αSMA antibody. C, Breast skin sections from 22- and 46-year-old female subjects probed with anti-progerin and lamin A. The respective double or triple merged signals are indicated.</p>", "links"=>[], "tags"=>["situ", "localization", "progerin", "sections", "derived", "hgps", "unaffected"], "article_id"=>611232, "categories"=>["Genetics", "Medicine", "Cell Biology", "Developmental Biology", "Molecular Biology"], "users"=>["Dayle McClintock", "Desiree Ratner", "Meepa Lokuge", "David M. Owens", "Leslie B. Gordon", "Francis S. Collins", "Karima Djabali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001269.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_situ_localization_of_progerin_on_human_skin_sections_derived_from_a_subject_with_HGPS_and_from_unaffected_individuals_/611232", "title"=>"In situ localization of progerin on human skin sections derived from a subject with HGPS and from unaffected individuals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:24:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/941071"], "description"=>"<p>Left panels correspond to anti-progerin monoclonal antibody staining of skin sections derived from individuals of indicated age. Right panels correspond to the merged signal of dapi and progerin signals. Square indicates the zoomed in region of the epidermis. ep denotes epidermis, and de the dermis.</p>", "links"=>[], "tags"=>["detection", "subset", "terminally", "differentiated"], "article_id"=>611488, "categories"=>["Genetics", "Medicine", "Cell Biology", "Developmental Biology", "Molecular Biology"], "users"=>["Dayle McClintock", "Desiree Ratner", "Meepa Lokuge", "David M. Owens", "Leslie B. Gordon", "Francis S. Collins", "Karima Djabali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001269.g005", "stats"=>{"downloads"=>1, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Progerin_detection_in_a_subset_of_terminally_differentiated_keratinocytes_/611488", "title"=>"Progerin detection in a subset of terminally differentiated keratinocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:26:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/940949"], "description"=>"<p>A, Forehead skin section from a 69-year-old individual probed with anti-progerin antibody and counterstained with dapi. Bars correspond to 100 and 50 µm, respectively. B, Forehead skin section from a 93-year-old donor. C, Skin sections from different body sites as indicated were probed with anti-progerin and anti- lamin A (LMNA) antibodies. Bar, 50 µm. Merged images are indicated.</p>", "links"=>[], "tags"=>["accumulation", "biopsy"], "article_id"=>611372, "categories"=>["Genetics", "Medicine", "Cell Biology", "Developmental Biology", "Molecular Biology"], "users"=>["Dayle McClintock", "Desiree Ratner", "Meepa Lokuge", "David M. Owens", "Leslie B. Gordon", "Francis S. Collins", "Karima Djabali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001269.g004", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Progerin_accumulation_in_human_elderly_skin_biopsy_sections_/611372", "title"=>"Progerin accumulation in human elderly skin biopsy sections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:25:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/940633"], "description"=>"<p>A, RT-PCR analysis of HGPS cells and human skin biopsies of indicated age, primers amplifying wild-type and progerin transcripts. B, Direct sequencing of a short portion within exon 11 of wild type lamin A (LMNA), and progerin transcripts from HGPS and 93-year-old subjects. C, Western blot analysis of protein extracted from skin biopsies of indicated age with anti-progerin 972S9, anti-lamin A/C and anti-actin antibodies.</p>", "links"=>[], "tags"=>["cell biology/cytoskeleton", "cell biology/gene expression", "cell biology/nuclear structure and function", "developmental biology/aging", "developmental biology/cell differentiation", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "molecular biology/rna splicing", "dermatology/photodermatology and skin aging"], "article_id"=>611049, "categories"=>["Genetics", "Medicine", "Cell Biology", "Developmental Biology", "Molecular Biology"], "users"=>["Dayle McClintock", "Desiree Ratner", "Meepa Lokuge", "David M. Owens", "Leslie B. Gordon", "Francis S. Collins", "Karima Djabali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001269.g001", "stats"=>{"downloads"=>2, "page_views"=>52, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Progerin_expression_in_human_skin_/611049", "title"=>"Progerin expression in human skin.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:23:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/941149"], "description"=>"<p>Classification of the skin biopsies originating from different body sites of unaffected individuals and collected at the Dermatology Department in accordance with the Columbia University Board protocols on human subject protection.</p><p>Total# 150 Samples</p>", "links"=>[], "tags"=>["cell biology/cytoskeleton", "cell biology/gene expression", "cell biology/nuclear structure and function", "developmental biology/aging", "developmental biology/cell differentiation", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "molecular biology/rna splicing", "dermatology/photodermatology and skin aging"], "article_id"=>611558, "categories"=>["Genetics", "Medicine", "Cell Biology", "Developmental Biology", "Molecular Biology"], "users"=>["Dayle McClintock", "Desiree Ratner", "Meepa Lokuge", "David M. Owens", "Leslie B. Gordon", "Francis S. Collins", "Karima Djabali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001269.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Human_skin_biopsies_/611558", "title"=>"Human skin biopsies", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 11:26:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/940714"], "description"=>"<p>A, Immunofluorescence microscopy on primary dermal fibroblasts from an HGPS subject and unaffected individuals of indicated ages with rabbit monoclonal anti-progerin antibody. B, Immunofluoresence detection of progerin in HGADFN 127 (HGPS individual) and DR118 (86-year-old individual) at late PPDs. C, Western blot analysis of nuclear protein extracts derived from fibroblast cultures HGADFN 127 (HGPS) at PPD 20 and DR118 (86-year-old female) at PPD 15 and 30, respectively, were immunoprecipitated with anti-progerin mAb 972S9 and the corresponding Western blot was probed with the same antibody.</p>", "links"=>[], "tags"=>["dermal", "fibroblast"], "article_id"=>611137, "categories"=>["Genetics", "Medicine", "Cell Biology", "Developmental Biology", "Molecular Biology"], "users"=>["Dayle McClintock", "Desiree Ratner", "Meepa Lokuge", "David M. Owens", "Leslie B. Gordon", "Francis S. Collins", "Karima Djabali"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001269.g002", "stats"=>{"downloads"=>1, "page_views"=>56, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Progerin_expression_in_primary_dermal_fibroblast_cultures_/611137", "title"=>"Progerin expression in primary dermal fibroblast cultures.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 11:24:04"}

PMC Usage Stats | Further Information

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Relative Metric

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