11/3/11 Study Suggests Way to Delay Age-Related Changes - WSJ.com

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HEALTH & WELLNESS NOVEMBER 3, 2011

For the first time, scientists showed in mice thatremoving a type of aging cell from the body that hasstopped dividing -- known as a senescent cell -- candelay or prevent age-related health issues. ShirleyWang has details on The News Hub.

By SHIRLEY S. WANG

Scientists may have found a way to put off some conditions of aging, according to a study in which theypostponed or even prevented such afflictions as cataracts and wrinkle-inducing fat loss in mice by removing cellsthat had stopped dividing.

Most young, healthy cells divide continuously in order to keepbody tissues and organs functioning properly, but eventuallystop splitting—a state called senescence—and are replaced byothers. Senescence occurs throughout life, but people's abilityto clear such cells from their bodies decreases with age, leadingto a buildup.

Researchers at the Mayo Clinic in Rochester, Minn., found forthe first time that by using a drug to target and kill senescentcells, they could essentially freeze some aspects of the agingprocess.

Though the research, published Wednesday in the journalNature, is in its very early stages, it suggests that senescent-cell

clearance could be one path to staying healthy while aging.

"If you could clear senescent cells, you perhaps could treat age-related diseases as a group rather thanindividually," said Jan van Deursen, senior author of the paper and a professor in the departments ofbiochemistry and pediatric and adolescent medicine at Mayo.

The importance of cell senescence to the aging process has long been suspected. But the latest findingdemonstrates definitively that these cells play a role in age-related conditions, according to Felipe Sierra,director of the division of aging biology at the National Institute on Aging, who wasn't involved in the study.

When cells become senescent, they produce harmfulcompounds such as those that cause inflammation. Chronictissue inflammation with aging is thought to underlie dementia,atherosclerosis and diabetes, among other ills, according toJames Kirkland, head of Mayo's Center on Aging, who was alsoan author of the study.

Senescent cells make up only a small portion of cells—some 5%or less—in the tissue of elderly people, but their effects can be

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Cell Study Finds a Way to Slow Ravages of Age

11/3/11 Study Suggests Way to Delay Age-Related Changes - WSJ.com

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Researchers found that by using a drug to target andkill senescent cells, they could essentially freezesome aspects of the aging process.

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widespread, the researchers said.

Because senescence is believed to have developed as a defenseagainst cancer, in which cells divide uncontrollably, simplyhalting the process could be dangerous.

But scientists have wondered for decades if the damageinflicted by senescent cells could be stopped if they wereremoved from the body altogether, or if the harmful substancesthey produced were neutralized.

In the study reported on Wednesday, the team used micedesigned to age faster than normal and treated them with adrug that identifies cells that have stopped dividing. The drugthen initiates the natural process that leads to cell death by

puncturing the membranes of those cells alone.

The researchers treated some mice over the course of their lifetimes and found a "quite dramatic delay" in thedevelopment of cataracts and age-related changes to muscle and fat, Dr. van Deursen said.

In other mice, the compound was administered in old age. Clearance of senescent cells in those mice didn'treverse the decline that had already occurred but prevented further deterioration.

The drug appeared to clear out only senescent cells, not normal ones, and the animals didn't appear to suffer anyside effects, the researcher said.

Extensive research is still necessary to test whether the clearance of senescent cells would have the same effect inmice that age normally and whether there are different effects in different tissues, such as the brain as comparedwith muscle tissue, said Dr. Sierra of the National Institute on Aging.

Another question is whether continuous clearance of senescent cells is needed to produce health benefits, orwhether intermittent removal—a spring cleaning of sorts—is just as effective, the study's authors said.

The work was funded by the Mayo Clinic, as well as several private foundations and philanthropists interested inpromoting research into aging.

Write to Shirley S. Wang at shirley.wang@wsj.com