SENS PubMed Publication Search
Longwave Ultraviolet Light Induces the Aging-Associated Progerin.
J Invest Dermatol. 2013 Feb 7. doi: 10.1038/jid.2013.71
Takeuchi H, Rünger TM
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 LaminA, 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 LaminA 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.
PMID: 23392295
Tags: damage identification, progerin