How Senescent Cells Spur Aging and Cancer (preview)

Feature Articles | Health See Inside

Cells that permanently stop dividing have long been recognized as one of the body's defenses against cancer. Now they are also seen as a sometime culprit in cancer and a cause of aging

By David Stipp ?| August 8, 2012

CELL SIGHTING: Investigators identify senescent cells?those that have lost the ability to divide?by their color. They turn blue when exposed to a particular chemical.

Image: Anatomy Blue

In Brief

• Senescent cells?which have permanently lost the ability to divide?were once assumed to contribute to aging by undermining tissue repair. Cells were thought to enter senescence to avoid becoming cancerous when damage put them at risk of proliferating uncontrollably.
• Later, the notion that senescent cells play a part in the aging of tissues and bodies fell out of favor. More recently, though, that idea has gained new support.
• Recent research indicates that the cells can contribute to aging in the originally proposed way and also by spurring inflammation. Plus, they can harm nearby cells in ways that promote cancer.
• Some evidence in mice suggests that retarding cellular senescence may help slow aging and delay some of the ills associated with it.

In 1999 JAN M. VAN deursen and his colleagues at the Mayo Clinic in Rochester, Minn., wanted to see whether mangled chromosomes cause cancer. So they engineered mice deficient in a protein that helps to maintain chromosomal integrity. The rodents' coils of DNA were duly deranged. Surprisingly, though, the animals were not particularly tumor-prone. Instead they developed a strange grab bag of ills, including cataracts, dwindling muscles, rapid thinning of fat under the skin and progressive spinal curvature, that made them look like one-humped camels. They also tended to die young.

Van Deursen had no idea why those particular abnormalities showed up. Then, in 2002, he spotted a report on mice afflicted by accelerated aging and was struck by photographs showing that their backs became humped as they aged. Suddenly, it hit him: his camel-backed mice, too, were aging unusually fast. Probing deeper, the Mayo team discovered that cells in a number of the rodents' tissues had prematurely slid into a state called cellular senescence, in which cells permanently lose the ability to divide and become aberrant in other ways. Such failure of cell division would explain the bone, muscle, eye and skin abnormalities observed by van Deursen's group.

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