Researchers have found a novel way of reversing the aging process. They found that a special category of cells, known as senescent cells, are bad actors that promote the aging of the tissues. Cleansing the body of the cells, they hope, could postpone many of the diseases of aging. This could pave the way for drugs that would keep human tissues healthier longer, but it is unclear until further testing is done whether such drugs could eventually help people live longer.
Most young, healthy cells divide continuously in order to keep body tissues and organs functioning properly, but eventually stop splitting—a state called senescence—and are replaced by others. Senescence occurs throughout life, but people's ability to clear such cells from their bodies decreases with age, leading to a buildup. Researchers explain that senescent cells accumulate in aging tissues, like arthritic knees, cataracts and the plaque that may line elderly arteries. The cells secrete agents that stimulate the immune system and cause low-level inflammation. Until now, there has been no way to tell if the presence of the cells is good, bad or indifferent.
In a feat of genetic engineering, a research team led by Darren J. Baker and Jan M. van Deursen at the Mayo Clinic in Rochester, Minn., has generated a strain of mouse in which all the senescent cells can be purged by giving the mice a drug that forces the cells to self-destruct.
The team reported online Wednesday in the journal Nature, that getting rid of the senescent cells the mice’s tissues showed a major improvement in the usual burden of age-related disorders. They did not develop cataracts, avoided the usual wasting of muscle with age, and could exercise much longer on a mouse treadmill. They retained the fat layers in the skin that usually thin out with age and, in people and cause wrinkling.
“I am very excited by the results,” said Dr. Norman E. Sharpless, an expert on aging at the University of North Carolina. “It suggests therapies that might work in real patients,” he said. Dr. van Deursen’s work is the first to show that removing senescent cells is beneficial. If confirmed, it “will be considered a fundamental advance by our field,” Dr. Sharpless said.
Judith Campisi, at the Buck Institute for Research on Aging, said the new finding was the first proof that senescent cells can drive the aging process. “So it’s really quite a breakthrough,” she said.
Dr. van Deursen said he thought it worth trying to eliminate senescent cells after the finding that they reliably switch on a characteristic marker gene known as p16-Ink4a. In his mice, he arranged that the genetic element that switches on the marker gene would also prime a mechanism to make the cell self-destruct. The mechanism fired only when the mice were dozed with a specific drug. The result was that only senescent cells were at risk from the drug, and that they could be purged at any desired time in the mouse’s lifetime.
In a second experiment, the mice were not given the cell-cleaning drug until they were middle-aged. Their cataracts had already developed by then and were irreversible, but aging was delayed in their fat and muscle tissues.
It may be that senescent cells are beneficial in youth but harmful in old age, when the immune system seems to clear them less rapidly from the body. The second mouse experiment suggests that middle age would be an effective time for clinical intervention, assuming humans behave in the same way.
:Therapeutic interventions to get rid of senescent cells or block their effects may represent an avenue to make us feel more vital, healthier, and allow us to stay independent for a much longer time,” Jan van Deursen said.
The Mayo Clinic finding “is a really important step forward for the field,” said Dr. Campisi of the Buck Institute. The purpose of research on aging, she said, is not to let people live a thousand years, as portrayed in science fiction, but to increase health span, the proportion of people’s natural lives that they live in good health.
“People used to see aging as a rusting nail — there’s nothing you can do about it,” Dr. Campisi said. “But we now know that there are processes that are driving aging, and that those processes can be meddled with.”
The work was funded by the Mayo Clinic, as well as several private foundations and philanthropists interested in promoting research into aging.
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