A natural anti-cancer mechanism that causes cells to stop dividing and go into limbo also drives the aging process, according to a study in mice that found removing the cells slows the physical decline that comes with age.
The breakthrough answers a riddle about the effect of the cells that refuse to die, though they no longer multiply, dodging scientists for five decades. The “deadbeat” cells, in a state known as senescence, accumulate over time and produce chemicals that damage tissue and trigger inflammation. The results, published yesterday in the journal Nature, show for the first time these cells play a pivotal role in the development of cataracts, muscle weakness and other byproducts of aging.
Researchers led by Jan van Deursen from the Mayo Clinic in Rochester, Minnesota, genetically engineered mice so they aged at five times the normal rate. Their senescent cells were also made sensitive to a normally harmless drug, enabling the researchers to destroy the cells with a medicine that did no damage elsewhere in the animal’s body.
“The clearance of these senescent cells, which are basically a byproduct of a mechanism to prevent us from developing tumors, improved the function of organs and tissues and in general led to better health,” said van Deursen, a molecular biologist and professor of cellular senescence, in a telephone interview. “We got more insight into why we age. Now that we know these senescent cells contribute to the process, we can think about ways to remove them.”
The area is ripe for exploration by pharmaceutical and biotechnology companies, van Deursen said. If researchers can find a drug that kills senescent cells, it may alter the way doctors approach diseases of the elderly, he said.
Currently, ailments such at cataracts or joint pain are treated separately. One therapy that can reverse the symptoms of aging could target the entire field, allowing a much broader and beneficial effect, he said.
“If you are successful at clearing the senescent cells, that would have a health benefit,” he said. “You could treat age-related disabilities as a group. That has advantages and makes it worth an investment.”
Investigators may also target the immune system to capitalize on the new findings. In the young, senescent cells are flushed by a strong immune system. As people age, their immune systems weaken and the ability to eliminate the cells diminishes, the researchers said. Now that it appears these cells are detrimental, doctors can look into strengthening the immune system so it is more powerful even at an advanced age.
Signs of Aging
The researchers examined the mice for cataracts, muscle wasting, strength and levels of fat deposits that shrink with age and cause wrinkles. Untreated mice had an aged and frail appearance, while those injected with the drug to kill the senescent cells seemed healthy and vital. They were less likely to have cataracts and more able to exercise, van Deursen said.
“An important goal isn’t just to extend life, but to improve the quality of life, especially at the end of life,” van Deursen said. “People can stay independent and active for a longer period of time, and reduce their dependence on the health-care system.”
The study used genetically engineered mice with senescent cells that carry a molecule called caspase 8. When the molecule was activated with drugs, it drilled a hole in the cells and killed them, according to scientists at the Mayo Clinic’s Robert and Arlene Kogod Center on Aging in Rochester, Minnesota.
“By attacking these cells and what they produce, one day we may be able to break the link between aging mechanisms and predisposition to diseases like heart disease, stroke, cancers and dementia,” said James Kirkland, the center’s head and a co- author of the report, in a statement.
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