Title |
The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin
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Published in |
PLOS ONE, December 2007
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DOI | 10.1371/journal.pone.0001269 |
Pubmed ID | |
Authors |
Dayle McClintock, Desiree Ratner, Meepa Lokuge, David M. Owens, Leslie B. Gordon, Francis S. Collins, Karima Djabali |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Japan | 3 | 1% |
United States | 2 | <1% |
Portugal | 1 | <1% |
India | 1 | <1% |
France | 1 | <1% |
Canada | 1 | <1% |
Finland | 1 | <1% |
Unknown | 262 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 64 | 24% |
Student > Bachelor | 54 | 20% |
Researcher | 41 | 15% |
Student > Master | 34 | 13% |
Student > Doctoral Student | 12 | 4% |
Other | 28 | 10% |
Unknown | 39 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 88 | 32% |
Biochemistry, Genetics and Molecular Biology | 83 | 31% |
Medicine and Dentistry | 19 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 2% |
Chemistry | 6 | 2% |
Other | 25 | 9% |
Unknown | 45 | 17% |