Tumor-Suppressor Genes Speed Up and Slow Down Aging in Engineered Mice

Scientists know that both these genes were expressed at increased levels as humans and mice age, but their role in the aging process was not clear. The study's findings demonstrated that p16 provides the impetus to accelerate cellular aging, while p19 stops that process.

The study‘s results, published May 30, 2008, in the online issue of Nature Cell Biology, could help give details into the development of some characteristics associated with aging, such as loss of muscle mass and strength or cataracts, and how they might be suppressed.

"Scientists interested in aging have developed mice that lack p16 or p19, but these mice were not suitable for studies on aging because they all die of cancer before they even begin to age,” reported the study's first author, Darren Baker, a laboratory technician at the Mayo Clinic (Rochester, MN, USA). "By crossing these mice with a mouse strain that ages five times faster than normal due to a mutation in the BubR1 gene, we were able to bypass this problem.”

Whereas other genes are involved in aging, the researchers clearly established that when too much p16 is produced, tissues start to age. Instead of driving aging, the p19 gene was discovered to neutralize the effects of p16. This was unexpected, according to Jan van Deursen, Ph.D., a molecular biologist at the Mayo Clinic, because tissue culture research had predicted that p19 expression promotes aging.

Another significant finding of the study is that initiation and progression of aging is caused, at least partly, by the accumulation of senescent or aging cells in tissues and organs. These senescent cells have an abnormal gene expression profile and secrete proteins that damage the surrounding cells, affecting tissue and organ function and aspects of aging.


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