Details

Autor(en) / Beteiligte

• McClintock, Dayle
• Ratner, Desiree
• Lokuge, Meepa
• Owens, David M
• Gordon, Leslie B
• Collins, Francis S
• Djabali, Karima
• Lewin, Alfred

Titel

The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin

Ist Teil von

• PloS one, 2007-12, Vol.2 (12), p.e1269-e1269

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.