A BOSTON GLOBE EDITORIAL

Backfiring genes

Tuesday, January 08, 2002

FOR SEVERAL YEARS, scientists trying to cure cancer with genetic therapy have placed hopes in one gene in particular, p53. Dubbed "the guardian of the genome," p53 suppresses the development of tumors, but in a mutated, weakened form leaves cells vulnerable to stress and more likely to become cancerous. Now it appears that whatever p53 does to block tumors might also speed the aging process.

Animal biology is replete with delicate balances of this kind in which a protective mechanism like the storing of energy in fat against the danger of scarcity can under some circumstances lead to obesity. Genes themselves often have Jekyll-Hyde functions: The same gene that causes sickle-cell anemia is known to protect against malaria. Still, it was disappointing for scientists to come up with new evidence that p53, while fending off tumors, also encourages signs of aging in mice, such as brittle bones, shrunken muscles, thinning hair.

The discovery, as described in the Jan. 3 issue of Nature, was serendipitous. Researchers at Baylor College of Medicine in Houston were trying to create mice with a weakened version of the p53 gene, but instead they inadvertently made mice with a strengthened version of it. Deeming the mice useless for the experiment at hand, the researchers set them aside, only to notice some time later that the rodents had begun to look prematurely aged.

In further experimentation, it was discovered that the mice with overactive p53 genes, even though they had few if any cancers, had lifespans 19 percent shorter than other mice. The researchers surmised that in its "guardian" role p53 ensures that cells' genetic instructions are copied accurately and, if not, p53 stops cells from growing and becoming, in some cases, tumors. While it is uncertain if the results would pertain to human beings, mice and humans are relatively close on the evolutionary tree.

An accompanying commentary in Nature pointed out some of the issues the new study raises. One is the possibility that persons treated with chemotherapy for childhood cancers might age prematurely, as a result of the p53 gene's proteins working overtime to cope with the extra cell stress. There is also the risk that attempts to use drugs to slow the process of aging might have the unintended side effect of spurring tumor growth.

From the lofty perspective of evolution, there is nothing really contradictory about a gene suppressing cancer and promoting aging. Normal functioning of p53 usually ensures that animals reach reproductive age without succumbing to aggressive cancers. After that, our genes are telling us, we are on our own. To avoid looking like the scrawny, thin-haired Baylor mice, physical and mental exercise and healthful habits generally might be a better prescription than tinkering with p53.

This story ran on page A12 of the Boston Globe on Tuesday, January 08, 2002.
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