Behind the creaky knees and forgetfulness of aging is a failure of tissues throughout the body to repair themselves when damaged. Scientists have wondered whether a dwindling supply of stem cells might help explain why this repair system falters with age. Now, three groups have bolstered this idea with research on a protein that keeps tabs on adult stem cells. Harnessing the discovery for antiaging potions may be a challenge, however: Blunting the protein also causes cancer.
In the late 1990s, several researchers found that a protein called p16ink4a, produced by a gene by the same name, increases dramatically in older tissues. In some cases, older mice had as much as 50 times more than younger ones. Scientists already knew that in as many as a third of human cancers, p16ink4a, known colloquially as p16, was mutated. At low levels, it allows cancer to proliferate; at high levels it suppresses tumors. In aging, however, its role was fuzzier. P16, it was thought, might grow more prevalent with age in order to prevent cancer to which an older mouse--or person--becomes more and more susceptible. But might it also be inhibiting tissue repair? Three teams set out to learn more.
The three focused on a smattering of adult stem cells that help various tissues regenerate when needed. Over time, these "progenitor cells" lose the ability to proliferate. One team, led by David Scadden of Harvard and Massachusetts General Hospital, studied hematopoietic stem cells, which form blood and immune cells; Sean Morrison of the University of Michigan, Ann Arbor, and his team looked at neural stem cells in the brain; and Norman Sharpless of the University of North Carolina, Chapel Hill, and his colleagues examined islet cells in the pancreas. All the groups tracked these cells in mice designed to lack p16.
In young animals, p16 deficiency didn't appear to matter much. In older animals, however, a lack of p16 prevented the decline in the number of progenitor cells. In the brain, for example, Morrison's group found that 1.3% of olfactory neurons in older mice without p16 were newly born—-nearly double the percentage found in control animals of the same age. Similar reversals were seen in islets and hematopoietic stem cells, but not in certain other cell types, the researchers report online 7 September in Nature.
The work is "very compelling," says Lawrence Donehower of Baylor College of Medicine in Houston, Texas. He has reported that mice with overactive p53, another tumor suppressor, age early, and is now studying p53's effects on hematopoietic stem cells. Because of the tradeoff between controlling cancer and preventing aging, "it's definitely going to be complicated" to apply this new work to age-related diseases, says Judith Campisi of the Lawrence Berkeley National Laboratory in California. "It's obviously extremely important to both fields," she says, but "we have a lot of work to do to sort this out."
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