Cancer-fighting, Longevity-promoting Gene Found

A gene that protects against cancer and environmental stress and promotes longevity has been identified in studies of a nematode worm, according to a report published last month in Science magazine.

The discovery by a research team at UC Santa Barbara provides scientists with a new means for identifying novel anticancer drugs and may lead to a better understanding of the effects of stress on longevity. It will make it possible to search for more potent and less harmful drugs that prevent or eliminate cancer using simple, easily cultured worms.

The human "p53" gene, the only gene to be featured on the cover of Newsweek, has been renowned for years as one of the most important genes in preventing cancer. In fact, most human tumors carry a defective p53 gene. However, notes Joel Rothman, professor of molecular biology and leader of the research team, "We found that p53 plays a more fundamental role in worms. It protects against the deleterious effects of cancer-causing agents and is apparently a kingpin for supporting life under a variety of stress conditions."

Though the studies on worms led the researchers to learn about p53 function in a whole animal, scientists initially did not believe that such a simple creature contained this gene. That changed when lead author William B. Derry, a post-doctoral fellow on Rothman's research team, discovered that worms carry the gene. "Although it was initially hard to recognize, we found that the worm gene has all the essential parts of the human cancer-blocking gene," said Derry.

Mammals, including humans, contain three forms of the p53 gene, which have some overlapping functions. The worm has only one such gene, making it possible for researchers to reveal what is the likely basic function of the family of p53 genes in all animals.

Most relevant to cancer is the worm gene's ability to protect against "genotoxic" stress, like the damaging exposure to carcinogens and radiation that leads to cancer cell growth in humans. Worm p53, much like its human counterpart, eliminates potential cancer cells by causing them to die while sparing healthy cells in the rest of the animal.

However, the UCSB team found, to their surprise, that the gene also extended the life span of worms that are starving.

Their discovery suggests that p53 may function to extend human life span, both by blocking cancer and possibly by protecting against the effects of environmental stresses. The scientists found that p53 helps the worm to survive in low oxygen levels, or asphyxiation. In humans, a lack of oxygen is responsible for the widespread tissue damage caused by heart attacks and stroke.

"The finding that p53 can protect worms against oxygen deprivation, starvation, and genotoxic stress indicates that it helps the animal react to quite different environmental stresses," said Rothman. Further, "these discoveries have implications for understanding human biology and also allow us to avail ourselves of genetics and biotechnology in worms to search for drugs--both therapeutic and preventive--that inhibit cancer in humans."

The team of scientists responsible for this work, which includes Derry, Rothman, and graduate student Aaron Putzke, discovered the worm p53 gene three years ago but learned of its function in stress and life span only in the past year.