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June 19, 2006
Volume 84, Number 25
p. 15

"The validity of the findings described in this article has been called into question by an internal investigative committee at the authors' university." See C&EN's Updated Coverage

Chemical Biology

Aging Cells Get New Lease On Life

Small molecule is found to extend lifetime of mammalian cells

Sarah Everts

We all face the inevitable, but new research is giving some cells a second chance. Korean researchers have found a complex thiourea derivative that can extend the lifetime of mammalian cells and reverse cellular aging.

CGK733 was discovered by screening a library of 20,000 synthetic molecules for their effects on aging cells (Nat. Chem. Biol., published online June 11, Tae Kook Kim and colleagues at Korea's Advanced Institute of Science & Technology report that CGK733 can extend the lifetime of cultured cells by approximately 20 divisions, or roughly 25%.

Kim Laboratory/Nature Chemical Biology

Clock Turned Back Aging cells (top left) can be revitalized (top right) by treatment with CGK733.

Biologists often call cell aging "senescence," a term that describes the physical and biochemical signs of a cell's deterioration toward death. These signals include a cessation of cell division, release of chemicals from the cell informing others of its impending demise, and an increase in the girth of the cell.

CGK733 is the first small molecule that can reverse aspects of cell senescence. Genetic techniques have been used to do so in the past. But what makes CGK733 unique is that its antiaging properties are reversible: When CGK733 is removed, cells return to normal aging and death.

This feature makes CGK733 more of a dimmer switch than an on/off switch and gives the molecule potential as a drug lead, Kim says. "Knocking out a protein's function entirely can lead to terrible side effects. The dimmer switch characteristic provides a window for dosage."

Kim hopes CGK733's antiaging properties will be useful in wound healing, antiaging cosmetics, and tissue engineering, a focus of current experimentation in his laboratory. His research team is now working on in vivo studies of the compound in animal models.

"There aren't any drugs out there that can reverse cellular senescence," says Steve Jackson, head of Cancer Research UK at the University of Cambridge. "This could be the tip of the iceberg for a whole range of studies over the next decade which might start delivering compounds that might delay, or one day reverse, some aspects of aging."

Jackson cautions that long-term health impacts of CGK733 need to be evaluated, as well as the compound's impact on other cell types and in animal models. CGK733 works by blocking a protein checkpoint involved in sensing and slowing down cells in response to DNA damage. Although Kim showed that cells whose aging was reversed by CGK733 didn't develop chromosomal abnormalities, the long-term effect of blocking DNA repair mechanisms could lead to cancer.

Cellular senescence researcher Judith Campisi of Lawrence Berkeley National Laboratory says CGK733 will be a good lab tool for biologists. "CGK733 is an example of what many scientists hope will be a trend: the identification of small molecules to mimic more cumbersome genetic interventions to regulate cellular behavior."

Chemical & Engineering News
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