For more than a decade, researchers have believed that aging cells damage the tissue around them, and that this damage underlies a number of age-related disorders. Now a new study in mice appears to confirm this. The study shows that selectively eliminating those aging, or “senescent,” cells, could help prevent the onset of everything from muscle loss to cataracts.
Senescent cells can no longer divide, and therefore fail to replenish aging tissue. More recently, researchers have suggested that these cells might be secreting damaging chemicals that poison the cells around them. To determine their role in the diseases of aging, scientists at the Mayo Clinic in Rochester, Minnesota, identified senescent cells in mice that had been genetically engineered to age rapidly using a biomarker, called p16Ink4a, specific to these cells. For the length of the animals’ lives, they were injected with a drug that induced only those biomarker-containing senescent cells to commit suicide, while leaving others untouched.
The results were striking: in tissues that contained the labeled cells, including everything from fat to muscle to eyes, selective removal appeared to postpone age-related damage. Treated mice had no cataracts, and showed increased muscle mass, strength, and subcutaneous fat when compared to mice that hadn’t received the drug.
“We’ve shown there is a causal link between these senescent cells and age-related decline in tissue function,” says Jan van Deursen, the Mayo Clinic cancer researcher who led the study. “It’s a proof of principle that if you remove this particular cell type from an organism—we did it in a mouse but it will probably hold true for humans—tissues and organs would function better and would be more resistant to aging.”
Prior to this study, it was unclear how senescent cells contributed to aging. The cells make up a very small proportion of all tissue, somewhere between 1 and 4 percent in even the oldest animals, and many doubted that such a small number of cells could have such a toxic effect. Rather, they thought, when the cells lost their ability to divide, the inability to replace lost tissue might be what caused symptoms of aging.
The new research appears to validate the idea of senescent-cell toxicity. “Now that we know the cells play a role in aging, it’s worth investing in trying to find a way to eliminate them,” says Felipe Sierra, the director of aging biology at the National Institute on Aging, who was not involved in the research.
Not only does the study propose a biomarker for aging, levels of p16Ink4a, but it validates the idea that it might be possible to create a drug that targets senescent cells without causing harm to healthy cells. “I’m cautiously optimistic that this is a really major advance,” says Norman Sharpless, a geneticist who studies cancer and aging at the University of North Carolina-Chapel Hill. “Their results suggest an approach that is within the reach of big pharma today.”
The current study used a mouse strain that had been genetically tweaked for rapid aging to speed up the experiment—because these mice tend to die early from other causes, the researchers were unable to determine whether increasing the animals’ “health span” would also increase their life span. Van Deursen and his colleagues are now beginning a more extensive study in normally aging mice in order to further investigate the effects of senescent-cell removal. Then, van Deursen says, “the challenge is to translate these findings into a way of getting rid of these cells in humans.”