Removing worn-out cells makes mice live longer and prosper

Killing worn-out cells helps middle-aged mice live longer, healthier lives, a new study suggests.

Removing those worn-out or “senescent” cells increased the median life span of mice from 24 to 27 percent over that of rodents in which senescent cells built up normally with age, Mayo Clinic researchers report online February 3 in Nature. Clearing senescent cells also improved heart and kidney function, the researchers found.

If the results hold up in people, they could lead to an entirely new way to treat aging, says gerontology and cancer researcher Norman Sharpless at the University of North Carolina School of Medicine in Chapel Hill. Most prospective antiaging treatments would require people to take a drug for decades. Periodically zapping senescent cells might temporarily turn back the clock and improve health for people who are already aging, he says. “If this paper is right, I believe it will be one of the most important aging papers ever,” Sharpless says.

Senescent cells are ones that have ceased to divide and do their usual jobs. Instead, they hunker down and pump out inflammatory chemicals that may damage surrounding tissues and promote further aging. “They’re zombie cells,” says Steven Austad, a biogerontologist at the University of Alabama at Birmingham. ”They’ve outlived their usefulness. They’re bad.”

Cancer biologist Jan van Deursen of the Mayo Clinic in Rochester, Minn., and colleagues devised the strategy for eliminating senescent cells by making the cells commit suicide. A protein called p16 builds up in senescent cells, the researchers had previously discovered. The team hooked up a gene for a protein that causes cells to kill themselves to DNA that helps turn on p16 production, so that whenever p16 was made the suicide protein was also made.

The suicide protein needs a partner chemical to actually kill cells, though. Once mice were a year old — 40 to 60 years old in human terms — the researchers started injecting them with the partner chemical. Mice got injections about every three days for six months. Mice that got the cell-suicide cocktail were compared with genetically engineered mice that were injected with a placebo mix.

Senescent cells were easier to kill in some organs than others, the researchers found. Colon and liver senescent cells weren’t killed, for instance. But age-related declines in the function of organs in which the treatment worked — eyes, fat, heart and kidney —were slowed.

Genetic engineering and regular shots would not be feasible for use in people, but several companies are developing drugs that might clear the zombie cells from humans, Austad says. Some side effects to the treatment in mice also would be important to consider if those drugs are ever used in people. Senescent cells have previously been shown to be needed for wound healing, and mice that got the killing cocktail couldn’t repair wounds as well as those that didn’t get the treatment. Once treatment stopped, the mice were able to heal normally again. That result suggests that people undergoing senescent-cell therapy might need to stop temporarily to heal wounds from surgery or accidents.

Previously, the researchers had killed senescent cells in mice with a mutation that caused them to age prematurely (SN: 12/3/11, p. 11). Removing the worn-out cells helped the prematurely old mice live longer, but other researchers weren’t convinced that the results applied to normal aging. “It’s great when you find something that helps prevent premature aging, but there’s always this nagging doubt,” says Judith Campisi, a researcher at the Buck Institute for Research on Aging in Novato, Calif. It’s gratifying that the treatment works to extend life and health in normally aging animals, she says.

Campisi also studies the effect of senescent cells on aging, but doesn’t think the cells are entirely to blame for the ills of old age. “We don’t believe senescence is the only thing that drives aging,” she says. “That would be stupid. If this were the magic bullet, Jan’s mice would live forever, but they don’t.”