AGING CELLS GET NEW LEASE ON LIFE
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CHEMICAL BIOLOGY AGING CELLS GET NEW LEASE ON LIFE Small molecule is found to extend lifetime of mammalian cells W Ε ALL FACE THE INEVITA- ble, but new research is giving some cells a sec- ond chance. Korean researchers have found a complex thiourea de- rivative 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 ef- fects on aging cells (Nat. Chem. Biol., published online June 11, dx.doi.org/10.1038/nchembio800). Tae Kook Kim and colleagues at Korea's Advanced Institute of Sci- ence & Technology report that CGK733 can extend the lifetime of cultured cells by approximately 20 divisions, or roughly 25%. 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 chemicalsfromthe cell inform- ing others of its impending de- mise, and an increase in the girth of the cell. CGK733 is the first small mol- ecule that can reverse aspects of cell senescence. Genetic tech- niques have been used to do so in the past. But what makes CGK733 unique is that its antiaging proper- ties 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 mole- cule potential as a drug lead, Kim says. "Knocking out a protein's function entirely can lead to ter- rible side effects. The dimmer switch characteristic provides a window for dosage." Kim hopes CGK733's antiag- ing properties will be useful in wound healing, antiaging cos- metics, 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 ani- mal models. "There aren't any drugs out there that can reverse cellular se- nescence," says SteveJackson, 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 as- pects 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 dam- age. Although Kim showed that cells whose aging was reversed by CGK733 didn't develop chromo- somal abnormalities, the long- term effect of blocking DNA repair mechanisms could lead to cancer. Cellular senescence research- er Judith Campisi of Lawrence Berkeley National Laboratory says CGK733 will be agoodlab tool for biologists. "CGK733 is an example ofwhat many scientists hope will be a trend: the identification of small molecules to mimic more cumbersome genetic interven- tions to regulate cellular behav- ior."-SARAH EVERTS CGK733 CLOCK TURNED BACK Aging cells (top left) can be revitalized (top right) by treatment with CGK733. EUROPEAN PHARMA Merck Capitulates On Bayer-Schering Deal w hat looked like a story that would turn into a long-running saga, with the an- ticipated merger of two German drug- makers being spoiled by a third, was resolved on the last day possible. Germany's Merck, which had acquired a 21.8% stake in Schering and thus threatened Bayer's agreement to acquire Scher- ing, agreed to offer its stake to Bayer. The agree- ment followed talks between Bayer and Merck and a lawsuit filed by Bayer against Merck, which will be withdrawn. The Merck stake, combined with the roughly 60% holding that Bayer already had, takes Bayer comfortably over the 75% target it had to attain by the end of the day on June U. Until Merck made the decision to offer its stake to Bayer, reaching that goal had looked unlikely. Now, however, Bay- er can complete its acquisition of Schering, as agreed upon in March when white knight Bayer outbid Merck's hostile offer for the Berlin-based pharmaceutical company. Merck began buying Schering shares on the stock market on June 9, in what it subsequent- ly said was a move to secure its long-term stra- tegic interest in Schering. That action effective- ly forced Bayer to start snapping up shares. By June 13, Bayer had purchased or been offered on- ly about 60% of Schering's shares, hence its de- cision to sue Merck in U.S. District Court in New York City for damages and to force Merck to divest its shares. Bayer is buying the Merck stake for 89 euros (roughly $115) per share, so it will pay the same price—effectively a 3.4% increase on its agreed- upon bid—for shares already purchased and those still outstanding.-PATRICIA SHORT WWW.CEN-0NLINE.ORG C&EN / JUNE 19, 2006 1 5 NEWS OF THE WEEK
Transcript of AGING CELLS GET NEW LEASE ON LIFE
C H E M I C A L B I O L O G Y
AGING CELLS GET NEW LEASE ON LIFE Small molecule is found to extend lifetime of mammalian cells
W Ε ALL FACE THE INEVITA-ble, but new research is giving some cells a sec
ond 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, dx.doi.org/10.1038/nchembio800). 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%.
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 agoodlab 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 behav-ior."-SARAH EVERTS
CGK733
CLOCK TURNED BACK Aging cells (top left) can be revitalized (top right) by treatment with CGK733.
E U R O P E A N P H A R M A
Merck Capitulates On Bayer-Schering Deal
w hat looked like a story that would turn into a long-running saga, with the anticipated merger of two German drug-
makers being spoiled by a third, was resolved on the last day possible. Germany's Merck, which had acquired a 21.8% stake in Schering and thus threatened Bayer's agreement to acquire Schering, agreed to offer its stake to Bayer. The agreement followed talks between Bayer and Merck and a lawsuit filed by Bayer against Merck, which will be withdrawn.
The Merck stake, combined with the roughly 60% holding that Bayer already had, takes Bayer comfortably over the 75% target it had to attain by the end of the day on June U. Until Merck made the decision to offer its stake to Bayer, reaching that goal had looked unlikely. Now, however, Bayer can complete its acquisition of Schering, as
agreed upon in March when white knight Bayer outbid Merck's hostile offer for the Berlin-based pharmaceutical company.
Merck began buying Schering shares on the stock market on June 9, in what it subsequently said was a move to secure its long-term strategic interest in Schering. That action effectively forced Bayer to start snapping up shares. By June 13, Bayer had purchased or been offered only about 60% of Schering's shares, hence its decision to sue Merck in U.S. District Court in New York City for damages and to force Merck to divest its shares.
Bayer is buying the Merck stake for 89 euros (roughly $115) per share, so it will pay the same price—effectively a 3.4% increase on its agreed-upon bid—for shares already purchased and those still outstanding.-PATRICIA SHORT
W W W . C E N - 0 N L I N E . O R G C&EN / JUNE 19, 2006 1 5
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