Brown University News Bureau

The Brown University News Bureau

1997-1998 index

Distributed September 29, 1997
Contact: Scott Turner

Brown researchers discover important piece of genetic aging puzzle

Brown researchers have endowed human cells with extended lifespans, making an inroad into the mysterious mechanism of aging. The findings have implications for tinkering with the aging process.

PROVIDENCE, R.I. -- A team of Brown University researchers has disrupted the natural progression of division and death in human cells, endowing the cells with an extended lifespan.

Reporting in the journal Science, Brown researchers describe how they can temporarily thwart the aging process by removing a gene, dubbed p21, from ordinary human cells cultivated in the lab. Cells without the gene divide up to 30 additional generations before dying.

The researchers modified a gene "knockout" method that is routinely used to genetically engineer mice for scientific research, and used the technology to remove the p21 gene from human cells. The "knockout" method described in Science allows for precise, specific changes in manipulating human cells.

"For obvious ethical and medical reasons, we can't make a knockout human, and we're not going to clone a human, so this is as close as we can get," said John Sedivy, associate professor of molecular biology, cellular biology and biochemistry. Because cancer cells appear to possess an infinite lifespan, the finding may offer insight into how human cells become tumor cells, an important step in understanding the cancer process, he said.

Moreover, the finding has broad disease-fighting implications because it allows scientists to study genetically varied human cells without altering human beings to produce such cells.

The preferred method of studying a gene's role is to remove it, eliminating its function. Knockout mice, for example, are used as models of human disease, such as cystic fibrosis, which can be induced in mice by removing one or more of their genes. Potential gene therapy treatment for cystic fibrosis involves implanting nonreproductive, or somatic, cells into people with the disease to introduce the missing genetic material.

The Brown research may have important gene therapy implications. "There is no reason we couldn't take cells from a patient, alter them, and put them back in that patient," said Sedivy, principal investigator of the Science paper with former postdoctoral associate Jeremy Brown and graduate student Wenyi Wei. "That's exactly what a lot of gene therapy trials are doing now, but they are using less sophisticated methods."

The Brown research also makes inroads into the mysterious mechanism of human aging. There are two general aging theories. First, that people grow old and die because their bodies wear out. Second, that a genetic program determines our lifespan.

"Compelling evidence exists that there is a genetic molecular clock in all cells in the body, irrespective of how you've taken care of yourself," Sedivy says. The Brown research has important implications for tinkering with the aging process.

"The findings are the best evidence yet that senescence, the mechanism behind growing old, is a real thing," Sedivy said. "We think we are looking at the molecular mechanism that actually determines senescence. Our goal is to understand and describe that mechanism."

However, the aging process is much more complicated than one gene's activities. "We probably have to alter a bunch of genes before human cells become immortalized," Sedivy said. "But we think this finding is an important incremental step, because there are probably not a lot of genes involved, maybe a half-dozen at most."

Editors: John Sedivy can be reached at (401) 863-7631.