A gene responsible for preventing cancer might also cause tissues to deline with age
Credit: United States Department of Health and Human Services
PARIS, 7 September 2006: A gene that prevents cells from becoming cancerous might also be to blame for tissue decline in the ageing process, U.S. researchers say.
The gene, called INKa, controls a protein whose role is to promote longevity by suppressing the development of cancer cells. But as the body ages, the gene becomes more and more active, eventually interfering with mechanims by which new, replacement cells are born to regenerate body tissue, according to three new studies.
"The good news is that we can get older before we get cancer," said Sean Morrison, director of the Centre for Stem Cell Biology at the University of Michigan, who lead-authored one of three parallel studies published this week in the British journal, Nature."The bad news is that our tissues can't repair themselves as well."
The research, conducted on laboratory mice, looked at levels of the gene's protein, called p16 INK4a, in several different areas that give birth to stem cells - the precursors of tissue-specific cells.
These areas were the brain's olfactory centre; the bone marrow, where blood cells are generated; and in the pancreas, the home of beta cells that make the hormone insulin. In each case, as the rodents aged, levels of p16 INK4a rose and stem cell renewal slowed.
Taking this discovery further, the scientists created "knockout" mice - mice that had been genetically modified to lack the INK4a gene. The mice retained their ability to regenerate cells. But they also died prematurely, from a wide range of cancers at only one year of age.
"The findings are remarkably consistent across the three papers," said Norman Sharpless, an assistant professor of medicine and genetics at the University of North Carolina, who led the work into the beta cells.
"Clearly, there are tissues where this gene doesn't play a role, but probably the effect is going to be much broader than in the few tissues we've identified."
Many avenues of exploration open out from this work, including the idea of a drug that would switch off the gene - or conversely, imitate its function.
"If you had a drug that could inhibit INK 4a function, you'd protentially have a therapy against degenerative diseases," said Morrison.
"But you'd have to watch patients carefully for cancers. By the same token, drugs that mimic INK4a function could be used to fight cancer."
INK4a does not work alone; indeed, it is likely to be only piece in a delicately-calibrated system.
It has an important upstream regulator - a gene called BMI-1 which promotes stem cell maintenance and cell regeneration but can also spur cancerous growth. To maintain themselves through adult life, stem cells balance their levels of both INK4a and BMI-1 proteins.
