Home Cellular health “Zombie cells” at the heart of the quest for an active and vital old age

“Zombie cells” at the heart of the quest for an active and vital old age


In an unfinished section of his basement, Richard Soller, 95, spins down an improvised track circling boxes filled with medals he won in track and field and long-distance running.

A few steps away is an expensive leather recliner he bought when he retired with visions of relaxation in old age. He proudly proclaims that he never used it; he’s been too busy training for competitions like the Senior National Games.

Soller has achieved an enviable goal pursued by humans since ancient times: to stay healthy and active at the end of life. It’s a goal that eludes so many people that aging is often associated with frailty and illness. But scientists are trying to change that — and tackle one of humanity’s greatest challenges — with a little-known but burgeoning area of ​​aging research called cellular senescence.

It is based on the idea that cells eventually stop dividing and enter a state of “senescence” in response to various forms of damage. The body eliminates most of them. But others linger like zombies. They are not dead. But as Nathan LeBrasseur of the Mayo Clinic says, they can damage nearby cells like moldy fruit spoiling a bowl of fruit. They accumulate in older bodies, which growing evidence links to age-related conditions such as dementia, cardiovascular disease and osteoporosis.

But scientists are wondering: can we stop the accumulation of zombie cells?

“The ability to understand aging — and the potential to intervene in the fundamental biology of aging — is truly the greatest opportunity we’ve had, perhaps in history, to transform human health,” says LeBrasseur.

With the number of people age 65 or older expected to double worldwide by 2050, cellular senescence is “a very hot topic,” says Viviana Perez Montes of the National Institutes of Health.

A hundred companies, as well as university teams, are exploring drugs to target senescent cells. And the research offers tantalizing clues that people could help tame senescence themselves by using Soller’s favored strategy: exercise.

Although no one believes senescence holds the key to a very long life, Tufts University researcher Christopher Wiley hopes for a day when fewer people suffer from age-related diseases.

“I’m not looking for the fountain of youth,” Wiley says. “I’m looking for the fountain not to be sick when I’m older.”

Leonard Hayflick, the scientist who discovered cellular senescence in 1960, is himself vital at 94. He is a professor of anatomy at the University of California, San Francisco and continues to write, present, and speak on the subject.

His scientific fame did not come easily. He discovered cellular senescence by accident, growing human fetal cells for a cancer biology project and noticing that they stopped dividing after about 50 population doublings. It wasn’t a big surprise; cell cultures have often failed due to things like contamination. What was surprising was that others stopped dividing at the same point. The phenomenon was later called “the Hayflick limit”.

The finding, Hayflick says, challenged the “60-year-old dogma” that normal human cells could replicate indefinitely. A paper he co-authored with colleague Paul Moorhead was rejected by a leading scientific journal, and Hayflick faced a decade of ridicule after it was published in Experimental Cell Research in 1961.

“It followed the usual pattern of major scientific discoveries, where first the discoverer is ridiculed, then someone says, ‘Well, maybe it works’…then it becomes accepted to some extent, then becomes more widely accepted,” says Hayflick.

Scientists say cellular senescence can be helpful. It likely evolved at least in part to suppress the development of cancer by limiting the ability of cells to continue dividing. It happens throughout our lives, triggered by things like DNA damage and the shortening of telomeres, the structures that cap and protect the ends of chromosomes. Senescent cells play a role in wound healing, embryonic development and childbirth.

Problems can arise when they accumulate.

“When you’re young, your immune system is able to recognize these senescent cells and eliminate them,” says Perez. “But when we start to age…our immune system activity also decreases, so we lose the ability to eliminate them.”

Experimental drugs designed to selectively kill senescent cells have been dubbed “senolytics,” and Mayo holds patents on some. In mice, they have been shown to be effective in delaying, preventing or alleviating several age-related disorders.

The possible benefits for people are just beginning to appear, and at least a dozen clinical trials with senolytics are now testing things like whether they can help control the progression of Alzheimer’s disease and improve the health of the skeleton.

Amid the buzz, some companies are marketing dietary supplements as senolytics. But the researchers warn that they have not been shown to work or be safe.

Today, LeBrasseur, who runs a center on aging in Mayo, says exercise is “the most promising tool we have” for healthy end-of-life functioning.

Research suggests that it counteracts the buildup of senescent cells. For example, a study conducted by LeBrasseur last year provided the first evidence in humans that exercise can significantly reduce indicators, found in the bloodstream, of senescent cell burden in the body.

Many older adults, like Soller, intuitively equate exercise with youth.

After a hamstring tear kept him from running in high school, Soller fell into an unhealthy lifestyle in early adulthood, smoking two packs of cigarettes a day. But he and his wife Jean quit when their daughter Mary arrived.

He started racing again just before he turned 50, and since then has raced in races across the United States and competed in decades of Senior Games competition. In May, Soller joined 12,000 like-minded athletes in Florida for the final national games in the Fort Lauderdale area – winning five medals to add to his collection of 1,500 awards.

Soller says exercise keeps him fit enough to deal with whatever comes his way.

“Do as much as you can,” he says. “That should be the goal for anyone to stay healthy.”