Mutation Slows Aging in Mice

A single mutation in a gene can lengthen a mouse's life by nearly a third without any noticeable harm, according to a study in today's Nature. The mutation changes the way the animals deal with toxic chemicals that damage DNA, the authors say.

A group led by oncologist Pier Guiseppe Pelicci of the European Institute of Oncology in Milan, Italy, had been studying a gene that can make any of three proteins, two of which are activated by growth factors. Wondering why the third protein, an enzyme called p66, was not, despite being very similar to the other two, Pelicci's team knocked out the piece of the gene that enabled it to code for p66, in order to make mice and mouse embryonic cells that lacked p66.

They found that without p66, cells were only half as likely to die when exposed to hydrogen peroxide (H2O2), a corrosive compound, or to ultraviolet light, both of which can oxidize and damage DNA. Apparently, p66 retards the cell's ability to deal with these stresses and instead causes damaged cells to die, Pelicci says. The team found a similar effect in whole mice lacking the enzyme. Because oxidative stress is thought to promote aging, the team also measured the mutant mice's life span. They found that the mutants lived 36 months, instead of the normal 28.

"It's a very important study because it provides further support for the idea that oxidative stress plays a role in aging," says Tomas Prolla, a geneticist at the University of Wisconsin, Madison. However, he says, "it's unclear if the rate of aging itself is retarded," as proof of that requires that the maximum life span be extended. But Pelicci hopes he's on the right track, and he is now working with gerontologists to see whether people who reach the century mark happen to lack p66.