Axing molecular zombies may slow aging

Killing off dormant cells in mice slows their decline

Cells that have stopped dividing but still linger in the body secrete harmful molecules that contribute to diseases related to aging, a new study in mice finds. Removing these dormant cells, called senescent cells, may help delay and even prevent many of the bothersome and painful ailments that afflict the elderly.

“Senescent cells act like demon seed and kill everything around them,” says physiologist James Kirkland of the Mayo Clinic in Rochester, Minn.These senescent cells menace their healthy neighbors and drive the biological processes that cause common age-associated maladies such as cataracts, loss of muscle mass and deterioration of the skin, Kirkland and his American and Dutch colleagues suggest online November 2 in Nature.

When a cell’s DNA becomes damaged by things like ultraviolet radiation or toxins, the cell will often enter a senescent state as a precautionary measure against the cancerous growth that can result from such damage. The immune system normally clears dormant cells from tissues. But as an organism ages, its tiring immune system begins to falter in the fight against these cellular zombies. As a consequence, senescent cells begin to accumulate in the older body, gaining strength in numbers.

“They won’t divide, but senescent cells are definitely not dead,” says Judith Campisi of the Buck Institute for Research on Aging in Novato, Calif., who was not involved in the study. Senescent cells may be the cellular equivalent of the walking dead, but they are still very metabolically active, Campisi explains. The molecules that senescent cells secrete can destroy normal tissue.

“People have known about senescent cells for 60 years,” says Kirkland, “but our study provides the first concrete example of a causal link between senescent cells and aging disorders.”

In a series of mouse studies, the researchers focused on a gene that is normally turned on in senescent cells but not healthy cells. The researchers altered the gene, called p16Ink4a, in a particular breed of fast-aging mice so the gene’s product would react with a synthetic drug and cause the cells to die rather than go dormant. Mice given the drug cleared their body tissues of senescent cells and had less age-related muscle loss, less thinning of skin and a lower rate of cataracts than mice that did not receive the drug. The results of the experiment suggested to Kirkland that “senescent cells can cause dysfunction in tissue and removing them can restore function.”

Kirkland and colleagues haven’t found the fountain of youth quite yet, but their study represents an important first step establishing the link between senescent cells and aging, says Campisi. She and Kirkland both say that the next step is to test the idea that senescent cells contribute to aging in mice — and perhaps humans — that age at a natural rate.

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