The central zombie cells in the pursuit of an active and vital old age

The central zombie cells in the pursuit of an active and vital old age

The central zombie cells in the pursuit of an active and vital old age

In an unfinished part of his basement, 95-year-old Richard Soller whizzes on a makeshift track that surrounds boxes full of medals he has won for track and field and long-distance running.

Without a hint of trouble, he says, “I can rack up miles down here.”

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

Soller, who lives near Cincinnati, has achieved an enviable goal pursued by humans since ancient times: to stay healthy and active into old age. It’s a goal that so many miss that getting old is often associated with becoming frail and sick. But scientists are trying to change this – and address one of humanity’s greatest challenges – through a little-known but thriving field of aging research called cellular senescence.

It is based on the idea that cells eventually stop dividing and enter a “senescent” state in response to various forms of damage. The body removes most of it. But others linger like zombies. They are not dead. But as Nathan LeBrasseur of the Mayo Clinic states, they can damage neighboring cells like moldy fruit corrupting a fruit basket. They accumulate in older bodies, and mounting evidence links to a number of age-related conditions such as dementia, cardiovascular disease and osteoporosis.

But scientists are wondering: Can the buildup of zombie cells be stopped?

“The ability to understand aging – and the potential to intervene in the fundamental biology of aging – is truly the greatest opportunity we have had, perhaps in history, to transform human health,” says LeBrasseur. The span of years in good health has an impact on “quality of life, public health, socioeconomics, the whole thing”.

With the number of people aged 65 and over expected to double globally by 2050, cellular senescence is “a very hot topic,” says Viviana Perez Montes of the National Institutes of Health. According to an Associated Press analysis of an NIH research database, there have been about 11,500 total projects involving cellular senescence since 1985, far more in recent years.

About 100 companies, as well as academic teams, are exploring drugs to target senescent cells. And the research offers tantalizing clues that people may be able to help tame senescence using Soller’s favorite strategy: exercise.

Although no one thinks senescence is the key to a super long life, Tufts University researcher Christopher Wiley hopes for a day fewer people will suffer fates like his late grandfather, who had Alzheimer’s and stared at him like he was a stranger.

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

DEAD CELLS

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.

At her beach house in Sonoma County, she browses a binder full of her research, including two first articles that have been cited a surprising number of times by other researchers. In front of him on the living room table are numerous copies of his seminal book, “How and Why We Age”, in various languages.

This scientific fame was not easy. He discovered cellular senescence by accident, growing human fetal cells for a cancer biology project and noting that they stopped dividing after about 50 population doublings. This wasn’t a big surprise; cell cultures often failed due to things like contamination. What was surprising was that others also stopped dividing in the same spot. The phenomenon was later called “the Hayflick limit”.

The discovery, Hayflick says, challenged the “60-year dogma” that normal human cells could replicate forever. An article he wrote with colleague Paul Moorhead was rejected by a major scientific journal, and Hayflick faced a decade of ridicule after being published in Experimental Cell Research in 1961.

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

At this point, he says, “the field I discovered has skyrocketed to an extent beyond my ability to keep up with it.”

BUILDING ZOMBIES

Scientists are careful to note that cellular senescence can be beneficial. It probably evolved at least in part to suppress the development of cancer by limiting the ability of cells to continue dividing. It happens throughout life, triggered by things like DNA damage and shortening of telomeres, structures that cover and protect the ends of chromosomes. Senescent cells play a role in wound healing, embryonic development and childbirth.

Problems can arise when they pile up.

“When you are young, your immune system is able to recognize these senescent cells and eliminate them,” says Perez, who studies cell biology and aging. “But as we start to age … the activity of our immune system also decreases, so we are losing the ability to eliminate them.”

Senescent cells resist apoptosis, or programmed cell death, and typically become large and flat, with enlarged nuclei. They release a mixture of molecules, some of which can trigger inflammation and damage other cells and, paradoxically, can also stimulate the growth of malignant cells and fuel cancer, says LeBrasseur.

Scientists link some ailments to accumulations of senescent cells in certain places. For example, research suggests that certain senescent cells that accumulate in lungs exposed to cigarette smoke may contribute substantially to airway inflammation in COPD.

The idea that one process can underlie numerous diseases is powerful for many scientists.

It inspired Dr. James Kirkland to transition from geriatric medicine. “I got tired of prescribing better wheelchairs and incontinence devices,” says Kirkland, a professor of medicine at Mayo who is considered a pioneer in the renaissance of senescence. “I wanted to do something more fundamental that could alleviate the suffering I’ve seen.”

OBJECTIVES OF THE DRUG

That research leads him and others to develop medicines.

Experimental drugs designed to selectively eliminate senescent cells have been dubbed “senolytics,” and Mayo owns the patents. In mice, they have been shown to be effective in delaying, preventing or alleviating several age-related ailments.

The possible benefits for people are just emerging. Kirkland, LeBrasseur and colleagues conducted a pilot study providing initial evidence that patients with severe lung disease could be helped by pairing a chemotherapy drug with a plant pigment. Another pilot study found that the same combination reduced the burden of senescent cells in the fat tissue of people with diabetic kidney disease.

At least a dozen clinical trials with senolytics are now testing things like they can help control the progression of Alzheimer’s, improve joint health in osteoarthritis, and improve skeletal health. Some teams are trying to develop “senomorphs” that can suppress the damaging effects of molecules emitted by senescent cells. And a Japanese team tested a vaccine in mice specific to a protein found in senescent cells, enabling their targeted elimination.

Scientists say serious work to improve human health could also bring marginal benefits, such as reducing skin wrinkles.

“I tell my lab that if we find a drug that cleans up the bad senescent cells and not the good ones and we treat Parkinson’s disease and Alzheimer’s and osteoporosis and macular degeneration, that would be wonderful,” says Judith Campisi, expert in biogerontology. at the Buck Institute for Research on Aging. “But if we cure wrinkles, we’ll get rich and I’ll never have to write another scholarship.”

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

And there is still a lot to learn about clinical trial drugs.

“We know that senolytics work quite well in mice,” says Wiley. “We’re still really trying to figure out the basics with people.”

‘MOST PROMISING TOOL’

Today, LeBrasseur, who heads an aging center in Mayo, says exercise is “the most promising tool we have” for good functioning in old age and its power extends to our cells.

Research suggests that it counteracts the accumulation of senescents, helping the immune system to release them and counteracting the molecular damage that can trigger the senescence process.

A study conducted by LeBrasseur last year provided the first evidence in humans that exercise can significantly reduce indicators of senescent cell load in the body in the bloodstream. After a 12-week aerobics, endurance, and balance program, the researchers found that older adults had lowered indicators of senescence and improved muscle strength, physical function, and reported health. A recently published review of research collects even more evidence – in animals and humans – for exercise as a targeted therapy for senescence.

Although such studies are not well known outside of scientific circles, many seniors intuitively equate exercise with youth.

Breeder Mike Gale, 81, set up an athletics circle on his sprawling property in Petaluma, California so he and a few friends could practice discus throwing and other equipment. Against the backdrop of rolling green hills, they twist, trample, throw and retrieve over and over again.

“I would love to compete at 90,” says Gale. “Why not?”

Soller asked himself a similar question a long time ago.

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

He started running again just before he turned 50, and has since participated in races in the United States, including two marathons, and has participated in decades of Senior Games competitions. In May, Soller joined 12,000 like-minded athletes in Florida for the latest national games in the Fort Lauderdale area, winning five medals to add to her collection of 1,500 awards.

Her daughter filmed her first place in the 200 meters from the stands, cheering: “Go, dad, go!”

Soller says exercise keeps him fit enough to handle whatever comes his way, including an Alzheimer’s diagnosis for his 62-year-old wife. Sometimes they walk the streets of the neighborhood together, holding hands.

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

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Video reporter Angie Wang contributed to this story.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

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