Stem cells: Old age proliferators 05/12/06. By the Wellcome Trust Age creeps up on all of us – including stem cells.

Stem cells must proliferate throughout adult life in order to repair tissues. However, the proliferation of stem cells also puts tissues at risk of cancer, so there is a delicate balance to be maintained. Stem cells strike this balance partly by reducing their ability to proliferate as the risk of cancer increases, but also by reducing the regenerative capacity of ageing tissues.

Three groups have now discovered that the p16INK4a protein regulates stem cell ageing. By altering the expression of p16INK4a, and then looking at the effects on mouse brain, pancreas and blood cells, they found that p16INK4a reduces stem cell proliferation, but only in older mice.

Although this effect of p16INK4a offers protection from cancer – as potential cancer cells are unable to proliferate – the decline in tissue regeneration is thought to contribute to some age-related diseases. By blocking p16INK4a, it may therefore be possible to mitigate the effects of ageing on certain tissues.

Above image: The forebrain of an adult mouse. With age, neural progenitor cells produce fewer new neurons (red), but deletion of the P16Ink4a gene can reduce this decline. Courtesy of Sean Morrison/University of Michigan.

References

Janzen V et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 2006;443(7110):421–6. Abstract

Krishnamurthy J et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 2006;443(7110):453–7. Abstract

Molofsky AV et al. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 2006;443(7110):448–52. Abstract