2007/12/05 by Dayle McClintock, Désirée Ratner, Meepa Lokuge +4 · 3 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Nuclear Structure and Function #RNA Research and Splicing #Retinoids in leukemia and cellular processes #Progeria #LMNA #Lamin #Biology #Papillary dermis #Premature aging #Dermis #Pathology #Cell biology #Cancer research #Genetics #Medicine #Anatomy #Gene
paper · pdf · doi:10.1371/journal.pone.0001269
openalex publication_date 2007/12/05 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.