Old Cells Advance Aging

By selectively killing senescent cells, researchers can slow the decline of health in aging mice.

By | November 2, 2011

An elderly manFLICKR, BLEU MAN

Researchers have been able to delay the onset of age-related health declines in mice by selectively killing off aging cells, suggesting that cellular senescence can actively causing damage to surrounding tissue. The findings, published today (November 2) in Nature, could one day be used to create anti-aging therapies.

“It’s been speculated for some time that these senescent cells are a major cause of what goes wrong with aging,” said molecular and cell biologist Judith Campisi of the Buck Institute for Research on Aging in Calif., who was not involved in the study. “So this is really a very important step forward in validating that hypothesis.”

Indeed, researchers have long recognized the role of senescent cells—aging cells which no longer divide—in the health decline that accompanies aging, such as muscle weakness, heart problems, cataracts, and other ailments. But it wasn’t clear whether aging cells cause harm because they actively secrete inflammatory molecules such as cytokines, or whether they were simply dead weight, harmful because they had lost their normal cellular functions, said Norman Sharpless, a gerontologist and oncologist at the University of North Carolina at Chapel Hill, who was not involved in the study.

To answer this question, cancer biologist Jan van Deursen of the Mayo Clinic and his colleagues developed a clever test.  Senescent cells, which often harbor genetic damage, secrete a tumor suppressor molecule called p16. Van Deursen and his team created mice that age prematurely, falling prey to a variety of age-related diseases early in life. They also inserted a gene into the mouse genome, which allowed them to selectively kill cells expressing p16 by feeding the mice rosiglitazone, a common diabetes drug.

Mice fed a diet containing rosiglitazone from infancy took much longer to develop muscle weakness, cataracts, and other signs of aging than controls. Even when older mice were fed rosiglitazone, many of the age-related problems plateaued. The findings suggest that senescent cells actively cause harm, and that killing them can delay at least some forms of aging. “If you translate that to humans, if you were to clear senescent cells regularly from a young age, that would probably have a major impact on health span,” van Deursen said.

Selectively killing off p16 didn’t slow all forms of aging, however. The treatment had no effect on the unusually high rates of heart disease seen in the mice. As a result, most mice still died of heart problems and the overall lifespan of the mice didn’t increase. In addition, the study looked at rapidly aging mice, but the researchers need to confirm that the same benefits occur in naturally aging mice, Campisi said.

Still, the study suggests a potential pathway for delaying aging in humans, Sharpless said. If cytokines and other inflammatory signals are the root of senescent cells’ adverse effects, “it’s not difficult to make drugs that interfere with [such signaling].” The trick would be determining which signals to target and ensuring that they don’t have undesirable side-effects, such as lessening people’s immune response to infection, he said.

D. J. Baker et. al, "Clearance of p16-Ink4a-positive senescent cells delays ageing-associated disorders," Nature, doi:10.1038/nature10600, 2011.

 

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Comments

Avatar of: Lara

Lara

Posts: 1457

November 3, 2011

For accuracy purposes, mice were not fed rosiglitazone, they were given AP20187 which induces the death of the p16ink4a expressing cells, rosiglitazone was used as an inducer of senescence in vitro

Avatar of:

Posts: 0

November 3, 2011

For accuracy purposes, mice were not fed rosiglitazone, they were given AP20187 which induces the death of the p16ink4a expressing cells, rosiglitazone was used as an inducer of senescence in vitro

Avatar of:

Posts: 0

November 3, 2011

For accuracy purposes, mice were not fed rosiglitazone, they were given AP20187 which induces the death of the p16ink4a expressing cells, rosiglitazone was used as an inducer of senescence in vitro

Avatar of:

Posts: 0

November 4, 2011

Well...so we come back to the old, good aspirin as a panacea... apart from its anti-inflammatory action, it would also help correcting "the heart problem" that the mice have :)

Avatar of:

Posts: 0

November 4, 2011

Well...so we come back to the old, good aspirin as a panacea... apart from its anti-inflammatory action, it would also help correcting "the heart problem" that the mice have :)

Avatar of: IwonaGrad

IwonaGrad

Posts: 13

November 4, 2011

Well...so we come back to the old, good aspirin as a panacea... apart from its anti-inflammatory action, it would also help correcting "the heart problem" that the mice have :)

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