May 2008

30 May 2008

Cell Biology: Cellular senescence and ageing

Nature Cell Biology doi: 10.1038/ncb1744

Two tumour suppressor genes with crucial effects on the ability of cells to divide and replicate have been found to affect the ageing process in mice. A report online this week in Nature Cell Biology demonstrates for the first time a direct link between the mechanisms of cellular senescence - the irreversible ceasing of cell replication - and ageing of the whole organism.

Mutant mice expressing low levels of the cell division protein BubR1 have been shown to undergo premature ageing characterized by a shorter lifespan, muscle atrophy and loss of fat. Of the tissues affected, skeletal muscle and fat accumulate high levels of the proteins p16Ink4a and p19Arf. Jan van Deursen and colleagues investigated the role of p16Ink4a and p19Arf genes in ageing by studying the consequences of their inactivation in BubR1-deficient mice. They found that elimination of p16Ink4a reduces both cellular senescence and premature ageing, whereas, in contrast, inactivation of p19Arf exacerbates these effects.

A role for the tumour suppressor genes p16Ink4a and p19Arf in ageing was previously suspected on the basis of findings that their expression increases with age; however, a direct involvement in the ageing process was never proven because mice lacking these genes die early of tumours.

Author contact:

Jan van Deursen (Mayo Clinic, Rochester, MN, USA)

Tel: +1 507 284 2524; E-mail:vandeursen.jan@mayo.edu

Opposing roles for p16^Ink4a and p19^Arf in senescence and ageing caused by BubR1 insufficiency

Darren J. Baker, Carmen Perez-Terzic, Fang Jin, Kevin Pitel, Nicolas J. Niederländer, Karthik Jeganathan, Satsuki Yamada, Santiago Reyes, Lois Rowe, H. Jay Hiddinga, Norman L. Eberhardt, Andre Terzic & Jan M. van Deursen

Published online: 30 May 2008; | doi:10.1038/ncb1744

Abstract | Full text

Other papers from Nature Cell Biology to be published online at the same time and with the same embargo:

WAVE and Arp2/3 jointly inhibit filopodium formation by entering into a complex with mDia2

Petra Beli, Debora Mascheroni, Dalu Xu & Metello Innocenti

Published online: 30 May 2008; | doi:10.1038/ncb1745

Abstract | Full text