ShareThisBy LEE BOWMAN
Three new studies show that a gene that suppresses tumor-cell growth also plays a key role in the aging of various types of cells and, if manipulated, could help treat some of the diseases of aging.
The researchers found that aging cells hold increasing concentrations of a gene called p16INK4a, and that the greater the expression of the gene, the poorer the function of the cells compared to young cells. They also found that those cells continued to behave as "old" cells even when they were transferred from old mice to young mice.
Separate teams from medical schools at the University of North Carolina at Chapel Hill, the University of Michigan and Harvard University reported their similar findings in studies of pancreatic islet cells, brain stem cells and blood stem cells. They reported their findings Thursday in three papers published in the journal Nature.
"The studies all indicate that certain stem cells lose their ability to divide and replace themselves with age as the expression of p16INK4a increases," said Dr. Norman Sharpless, an assistant professor of medicine and genetics at UNC and co-author of all three studies.
He and a UNC colleague, Dr. Janakiraman Krishnamurthy, patented the use of the gene as a biomarker in human aging two years ago.
The gene also is known to stop cancer cells from dividing and is more likely to be expressed with aging. To better understand its effects, the researchers developed strains of mice that were either deficient in the gene (it was deleted from their genetic code) or genetically altered to produce an excess of the protein expressed by the gene, making cells in the mice age prematurely.
Sharpless said that in the mice lacking the aging gene, islet cells continued to proliferate as the animals aged, "almost as if they were younger animals." But in mice bred with an excess of the gene, "islet cells aged prematurely; they stopped dividing early," he said.
"This suggests that if we could attenuate p16INK4a expression in some way in humans, it could lead to enhanced islet re-growth in adults and a possible new treatment for diabetes," Sharpless added.
Similar results were seen in the neural stem cells of mice studied by the Michigan team and in blood stem cells of mice studied by researchers at Harvard.
The Harvard team, led by Dr. David Scadden, also showed that blood stem cells from old mice lacking the gene functioned better than similar old cells from wild-type mice with ordinary levels of the gene, suggesting that it causes aging in those cells, too.
Sharpless said while there is clearly promise for therapy that might eventually benefit humans in the findings, knocking out the gene as a cure for aging is not possible, since the mice lacking the gene didn't live any longer, and developed more cancers than old, normal mice.
He added that "in all three studies, p16INK4a loss was associated with an improvement in some but not all the consequences of aging. There are clearly things in addition to p16INK4a that contribute to aging. We don't know what they are."
Still, he expects that as a way to measure the pace of aging in cells, the gene should be useful almost immediately.
"If you were going to calorically restrict yourself or take green tea of resveratrol (a compound found in grapes and other plants that inhibits cell damage) every day for years in an effort to prevent aging, wouldn't you like some evidence that these not entirely benign things were having a beneficial effect?
"Now, we have a biomarker that can directly test the effects of such things,'' Sharpless said.
On the Net: http://www.nature.com
