title: Longwave UV light induces the aging-associated progerin.
abstract: Premature aging in Hutchinson-Gilford progeria syndrome (HGPS) is caused by a mutation of the LMNA gene that activates a cryptic splice site. This results in expression of a truncated form of Lamin A, called progerin. Accumulation of progerin in the nuclei of HGPS cells impairs nuclear functions and causes abnormal nuclear morphology. Progerin accumulation has not only been described in HGPS, but also during normal intrinsic aging. We hypothesized that accumulation of progerin with abnormal nuclear shapes may also be accelerated by UV and with that contribute to photoaging of the skin. We exposed neonatal or aged cultured fibroblasts to single or repeated doses of longwave or shortwave UV (UVA or UVB) and found that UVA, but not UVB, induces progerin expression and HGPS-like abnormal nuclear shapes in all cells, but more in aged cells. The induction of progerin is mediated by UVA-induced oxidative damage and subsequent alternative splicing of the LMNA transcript, as progerin induction was suppressed by the singlet oxygen quencher sodium azide, and as mRNA expression of LMNA was not induced by UVA. These data suggest a previously unreported pathway of photoaging and support the concept that photoaging is at least in part a process of damage-accelerated intrinsic aging.
authors: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Hirotaka
authors: H
authors: Takeuchi
authors: Thomas M
authors: TM
authors: Rünger
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology / Q000528:radiation effects*; D002648:Child; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D007231:Infant, Newborn; D034904:Lamin Type A; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D011371:Progeria / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D015595:Skin Aging / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A