One hallmark of aging is the inability to heal as fast or maintain tissues and organs as well as in youth. These processes rely on stem cells, the immortal precursors of all the body's tissues, so failures in repair and regeneration could result from the failure of stem cells to renew themselves. The details of stem cell aging have remained mysterious, though.
Recently several groups had noticed that a protein called p16Ink4a accumulates in stem cells over time, suggesting a role in their longevity. To test for its function, they deleted its gene from mice. Strangely, these mice tended to die from assorted cancers by the relatively young age of one. (Old age in mice is three years.) When researchers allowed the surviving mice to grow old, however, they noted something even more remarkable: the rodents had double the usual rate of new brain cell growth in their forebrains (neurons in red above; supporting cells in green) and similarly milder than normal declines in the proliferation of blood cells and pancreatic islet cells, which produce insulin. Overexpressing Ink4a in young mice also cut down the number of islet cells, effectively aging the mice prematurely. "This is the first mechanistic insight into why stem cells age. The data suggest that Ink4a plays a widespread role," says stem cell researcher Sean Morrison of the University of Michigan, whose group as well as two others publish online September 6 in Nature. Other experts are equally impressed. "They are the first to show you could restore some of stem cells' potential," says Christian Beausjour of the University of Montreal.
The researchers hypothesize that the protein protects against cancer by preventing stem cells from reproducing in old age, when they may have accumulated many genetic defects that would tend to produce cancer. Deactivating the protein for years at a time in people would therefore be risky, although a drug that briefly counteracted its effects might promote wound healing in the elderly, Morrison points out.