Team finds that turning on tumor suppressor in immature mice triggers premature aging.

U.S. scientists have uncovered a seemingly causal role for the tumor suppressor protein p16 in the process of aging. The Fox Chase Cancer Center team developed a mouse model in which p16 expression can be turned on or off in different tissues and at different times in its life. They found that triggering p16 expression blocked cell proliferation and induced signs of premature aging in even immature animals. The team claims its mouse model is the first to demonstrate characteristics of premature aging without any associated macromolecular damage. Their research is being presented at the AACR 102nd Annual Meeting today.

“The p16 protein has been previously associated with aging, and we know its expression increases during late stages of aging, but the idea that its expression would be sufficient to generate features of aging was surprising,” states lead researcher, Greg H. Enders, M.D., associate professor for the Fox Chase’s epigenetics and progenitor cell program. Although previous work has shown that p16 accumulates in tissues as they age, the new data suggest the protein has a causal role in the aging process rather than an associated role. “What this suggests to us is that p16 may be an effector of aging, not just a marker of aging tissues,” Dr. Enders adds. The researchers in addition say they have early evidence that the features of premature aging in immature mice can be reversed by turning off p16.

To try and find out how p16 was involved in aging, the Fox Chase team looked at the intestines of wild-type and engineered mice. They found that p16 accumulated in tissue stem cells and blocked them from dividing. Expression of the protein also reduced cancer formation in a mouse model of intestinal cancer. These combined observations led the researchers to suggest that p16 blocks tumor formation by holding back the proliferation of precancerous stem cells as well as cancerous cells.  

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