Cging is a cost of cancer protection

[flying_unicorn]

Findings suggest that aging is a cost of cancer protection

WASHINGTON POST - A critical protein that protects animals from cancer in their early years appears to also cause much of the deterioration associated with aging, according to a provocative new study.

The findings, by scientists at the Baylor College of Medicine in Houston, ''raise the shocking possibility that aging may be a side effect of the natural safeguards that protect us from cancer,'' two commentators say in an editorial accompanying the study, which appears in today's edition of the journal Nature.

The research was done in mice, and its applicability to people is uncertain. But mice and humans are close evolutionary relatives, and the study will probably set off a race to clarify the relationship between cancer biology and aging in humans.

Bert Vogelstein, a cancer researcher at Johns Hopkins University, said the results were fascinating and surprising. ''Like all good research, it raises a lot more questions than it answers,'' he said.

Among the questions is whether any attempt to slow down the overall process of aging would raise cancer rates. The Nature commentary says that scientists working on aging now have to take into account the prospect that ''drug-related approaches to interfere with this process may come at a price, the disruption of our natural mechanisms for keeping cancer at bay.''

The research also raises the possibility that younger people treated successfully for cancer with chemotherapy may be subject to premature aging later in life, a possibility that has never been rigorously examined. The Nature commentators, Gerardo Ferbeyre and Scott W. Lowe, called for immediate study of that possibility.

The new paper started with an apparent failure in the laboratory. Eight years ago, in the cancer lab of Lawrence Donehower at Baylor College of Medicine, researchers were trying to create mice with a weakened version of a protein called p53, which is a central cog in the machinery that prevents cells from growing wildly out of control and turning into tumors.

The hope was that the mice in the study would be susceptible to tumors similar to those in human patients. But the techniques for manipulating genes are still crude, and instead of making mice with weakened p53, Donehower and colleagues made mice with a hyperactive version of the protein.

Exasperated, they figured that the mice wouldn't do them much good in their cancer work. ''We sort of set the mice off in a corner of our mouse colony and ignored them,'' Donehower said.

Even ordinary mice are fairly prone to develop tumors, and the researchers noticed that virtually none of the mutant mice were getting tumors. That was not surprising, because p53 is known to be an effective tumor suppressor.

But as time went on, the tumor-free mice looked weirder and weirder. ''I couldn't quite figure out what it was until my lab technician, Ben Cooper, said the words, `These mice just look old,''' Donehower recalled. ''That was like a light bulb.''

A young graduate student, Stuart Tyner, grabbed hold of the project. ''I felt like this was kind of a gold mine,'' Tyner said. He subjected the mutant mice to a battery of tests that confirmed what was obvious to the naked eye: They were fading fast.

At an age when normal mice are still fairly vigorous, the bones of the mutant mice became brittle and porous, and they developed hunchbacks. Their hair thinned. Their muscles and other body parts shrank. They lost weight. They recovered poorly from wounds and other stresses.

Even though virtually none of them came down with cancers, they died, on average, at 96 weeks, compared to 118 weeks for a population of normal mice. Their enhanced cancer resistance was accompanied, in other words, by a 20 percent drop in life span.

The work confirms hints that had been emerging in the scientific literature that p53 and related proteins might play an important role in aging.

But the new paper is far more detailed - and, scientists say, more compelling - than anything published to date.