Nuclear swelling occurs during premature senescence mediated by MAP kinases in normal human fibroblasts.

Excess thymidine induced premature senescence in normal human fibroblasts (TIG-7), with induction of typical senescence markers. Nuclear swelling, as well as cell swelling, was clearly observed in these senescent cells. Simultaneous addition of MAP kinase inhibitors, U0126, SB203580, and SP60025, effectively suppressed induction of premature senescence and senescence markers.

G-protein gamma subunit GNG11 strongly regulates cellular senescence.

GNG11 is a member of the gamma subunit family of heteromeric G-protein, but its function is entirely unknown. Here, we successfully characterized its specific role in cellular senescence. We have found that overexpression of GNG11 immediately induces cellular senescence in normal human fibroblasts, and its down-regulation by antisense cDNA extends their lifespan.

Prolonged unbalanced growth induces cellular senescence markers linked with mechano transduction in normal and tumor cells.

Cellular senescence is induced by diverse means and hence thought to be mediated by multiple pathways. We show that prolonged unbalanced growth due to retardation of DNA replication elicits a senescence-like phenomenon irrespective of the cell type. In fact, modest inhibition of DNA replication by various means led to cell swelling, cytoskeletal alterations, and irregularly enlarged, flat cell shape.