Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts.

ABSTRACT: Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disease, is caused by a point mutation in the lamin A gene (LMNA). This mutation constitutively activates a cryptic splice donor site, resulting in a mutant lamin A protein known as progerin. Recent studies have demonstrated that progerin is also produced at low levels in normal human cells and tissues. However, the cause-and-effect relationship between normal aging and progerin production in normal individuals has not yet been determined. In this study, we have shown in normal human fibroblasts that progressive telomere damage during cellular senescence plays a causative role in activating progerin production. Progressive telomere damage was also found to lead to extensive changes in alternative splicing in multipl

SUBMITTER: Cao K 

PROVIDER: S-EPMC3223819 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature