Taming natural cell death for longer life
In his basement, 95-year-old Richard Soller zips around a makeshift track encircling boxes full of medals he’s won for track and field and long-distance running.
Without a hint of breathlessness, he says, “I can put in miles down here.”
Steps away is an expensive leather recliner he bought when he retired from Procter & Gamble with visions of relaxing into old age. He proudly proclaims he’s never used it. He’s been too busy training for competitions, such as the National Senior Games.
Soller has achieved an enviable goal: staying healthy and active in late life. Growing old is often associated with getting frail and sick. But scientists are trying to change that — and tackle one of humanity’s biggest challenges — through a little-known but flourishing field of aging research called cellular senescence.
When cells get old
It’s built upon the idea that cells eventually stop dividing and enter a “senescent” state in response to various forms of damage. The body removes most of them.
But others linger like zombies. They aren’t dead. But as the Mayo Clinic’s Nathan LeBrasseur puts it, they can harm nearby cells like moldy fruit corrupting a fruit bowl.
They accumulate in older bodies, which mounting evidence links to an array of age-related conditions such as dementia, cardiovascular disease and osteoporosis.
But scientists wonder: Can the zombie cell buildup 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, maybe in history, to transform human health,” LeBrasseur said. Extending the span of healthy years impacts “quality of life, public health, socioeconomics, the whole shebang.”
With the number of people 65 or older expected to double globally by 2050, cellular senescence is “a very hot topic,” said Viviana Perez Montes of the National Institutes of Health.
According to an Associated Press analysis of an NIH research database, there have been around 11,500 total projects involving cellular senescence since 1985, and far more in recent years.
About 100 companies, plus academic teams, are exploring drugs to target senescent cells. And research offers clues that people may be able to help tame senescence themselves using the strategy favored by Soller: exercise.
Although no one thinks senescence holds the key to super long life, Tufts University researcher Christopher Wiley hopes for a day when fewer people suffer fates like his late grandfather, who had Alzheimer’s and stared back at him as if he were a stranger.
“I’m not looking for the fountain of youth,” Wiley said. “I’m looking for the fountain of not being sick when I’m older.”
The good side of senescence
Scientists are careful to note that cell senescence can be useful. It likely evolved at least in part to suppress the development of cancer by limiting the capacity of cells to keep dividing.
It happens throughout our lives, triggered by things like DNA damage and the shortening of telomeres — structures that cap and protect the ends of chromosomes.
Senescent cells play a role in wound healing, embryonic development and childbirth. Sill, problems can arise when they build up.
“When we start getting old, the activity of our immune system also gets diminished, so we’re losing the capacity to eliminate them,” Perez said.
Scientists link some disorders to buildups of senescent cells in certain spots. For example, research suggests senescent cells that accumulate in lungs exposed to cigarette smoke may contribute substantially to airway inflammation in Chronic Obstructive Pulmonary Disease (COPD).
The idea that one process could be at the root of numerous diseases is powerful to many scientists.
Drug that may help
Experimental drugs designed to selectively clear senescent cells have been dubbed “senolytics,” and Mayo holds patents on some. In mice, they’ve been shown to be effective at delaying, preventing or easing several age-related disorders.
Possible benefits for people are just emerging. Dr. James Kirkland, LeBrasseur and colleagues did a pilot study providing initial evidence that patients with a serious lung disease might be helped by pairing a chemotherapy drug with a plant pigment.
Another pilot study found 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 whether they can help control Alzheimer’s progression, improve joint health in osteoarthritis, and improve skeletal health.
Some teams are trying to develop “senomorphics” that can suppress detrimental effects of molecules emitted by senescent cells. And a Japanese team has tested a vaccine on mice specific to a protein found in senescent cells, allowing for their targeted elimination.
Scientists say serious work to improve human health could also bring fringe benefits, like reducing skin wrinkling.
“I tell my lab that if we find a drug that clears the bad senescent cells and not the good ones and we cure Parkinson’s disease and Alzheimer’s and osteoporosis and macular degeneration, it would be wonderful,” said Judith Campisi, a biogerontology expert at the Buck Institute for Research on Aging. “But if we cure wrinkles, we’ll be rich, and I’ll never have to write another grant.”
Amid the buzz, some companies are already marketing dietary supplements as senolytics. But researchers warn they haven’t been shown to work or been proven safe.
Exercise is ‘most promising tool’
Today, LeBrasseur, who directs a center on aging at Mayo, said exercise is “the most promising tool that we have” for good functioning in late life, and its power extends to our cells.
Research suggests it counters the buildup of senescent ones, helping the immune system clear them, and counteracting the molecular damage that can spark the senescence process.
A study LeBrasseur led last year provided the first evidence in humans that exercise can significantly reduce indicators, found in the bloodstream, of the burden of senescent cells in the body.
After a 12-week aerobics, resistance and balance training program, researchers found that older adults had lowered indicators of senescence and better muscle strength, physical function and reported health.
A recently-published research review collects even more evidence — in animals and humans — for exercise as a senescence-targeting therapy.
While such studies aren’t well known outside scientific circles, many older adults intuitively equate exercise with youthfulness.
Soller said exercise keeps him fit enough to handle what comes his way. “Do as much as you can,” he said. “That should be the goal for anyone to stay healthy.”