The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin.
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.
Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
Dayle
D
McClintock
Desiree
D
Ratner
Meepa
M
Lokuge
David M
DM
Owens
Leslie B
LB
Gordon
Francis S
FS
Collins
Karima
K
Djabali
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism*; D016922:Cellular Senescence / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000276:immunology; D011371:Progeria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000276:immunology; D012867:Skin / Q000473:pathology*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D017931:DNA Primers; D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A