Turn back time

One type of exercise “reverses” aging’s effect on stem cells — study

Aging takes a toll on your muscle tissue. Researchers discover one type of activity puts this process in reverse.

As people age, they lose muscle mass and the risk of heart disease, dementia, and reduced immune function increases. As the years tick by, it becomes harder for people to bounce back from a workout, injury, or illness.

Consistent exercise can slow down this degenerative process — but a new study suggests we may not have to settle for slowing down. According to new research in mice, aerobic exercise may actually reverse aging’s effect on essential muscle stem cells involved with tissue regeneration.

If the research translates to humans, it means jogging, swimming, cycling, and other aerobic activities can help older people recover as quickly and efficiently as their younger selves. In the far future, these results could inform the creation of a drug that de-ages muscle stem cells.

This finding was published Monday in the journal Nature Metabolism.

Researchers have known for a long time that exercise promotes healthspan, giving people extra disease-free years.

This discovery is “very different,” co-author Thomas Rando, a neurology researcher at Stanford University, tells Inverse.

“This is like taking, in a sense, a person who has already aged and acquired these diseases, and then reversed that process," Rando explains.

This study suggests that aerobic exercise can cause old cells to behave more like — and gain the characteristics of — young cells. To get there, the scientists rounded up young and old mice and gave them access to a running wheel for three weeks. Then, with a battery of tests, they analyzed how the mouse's muscle stem cells and muscle tissue responded.

They compared the mouse runners to a group of non-exercising mice who were given a locked wheel and no opportunity to run.

Within a single week, both young and old mice with the running wheels established a routine, running about 10 and 4.9 kilometers per night, respectively.

The human equivalent to the mice running wheel regime would likely be regular, aerobic exercise— swimming, running, cycling, Rando says. Not strength training or weight lifting.

New research suggests aerobic exercise — like swimming — can kick-start old, dormant muscle stem cells.

Alexander Rhind

After three weeks of voluntary wheel running, the mice were moved to cages without any wheels. Then, the researchers injured certain muscles and analyzed how the mice rebuilt the injured tissue.

They also transplanted muscle stem cells from old mice into other injured mice, and saw how well the cells functioned. Compared with young donor muscle stem cells, old donor muscle stem cells formed smaller and fewer fibers in the injured mice. But old muscle stem cells from exercising mice performed like young muscle stem cells, forming more fibers than non-exercising old muscle stem cells.

Overall, older mice who exercised experienced improved muscle stem cell function and accelerated muscle tissue repair.

The active, older mice didn't produce more muscle stem cells. Instead, exercise had a “rejuvenating” effect on old cells, Rando says. It triggered a Benjamin Button-effect and helped mice operate more like their younger selves.

These benefits disappeared one week after the mice stopped running, suggesting that what causes the rejuvenating effect is sustained exercise.

This implies that voluntary aerobic exercise may have benefits "above and beyond" the prevention of age-related diseases, and may actually improve tissue function directly, Rando says.

"The idea would be that that older individuals would recover faster and more efficiently like young people do in response to an injury," he explains

Surprisingly, young mice who ran the wheel did not experience improved muscle repair. This puzzled Rando and his team.

"It's as if young mice have already kind of plateaued," Rando explains. "They lose function with age and they can get back to that baseline, but it's hard to make them still better with more exercise."

Exercise’s effects on muscle stem cells and tissue repair come down to a tiny protein called cyclin D1, the study explains. Voluntary aerobic exercise restored cyclin D1 levels in dormant stem cells back to youthful levels, effectively accelerating muscle stem cell regeneration.

Discovering cyclinD1's critical role means researchers may be able to target the protein therapeutically or develop a drug that creates these positive de-aging effects, the researchers say.

But before any kind of anti-aging pill or prescribed exercise-regime comes down the pipeline, more research in humans is needed.

Longevity Hacks is a regular series from Inverse on the science-backed strategies to live better, healthier, and longer without medicine.

HOW THIS AFFECTS LONGEVITY — As people age, it becomes increasingly difficult to repair muscle tissue and bounce back from a tough workout or injury. According to this new study, regular, aerobic exercise can reverse aging's toll on critical muscle stem cells involved in this process.

WHY IT’S A HACK — Previous research shows exercise can slow aging's de-generative effect on muscle stem cells, but this study shows it may reverse these impacts. If the study's findings are replicated in humans, that means regular, aerobic exercise could keep people active later in life, perform more like their younger selves athletically, and make them more resilient to injury.

SCIENCE IN ACTION — In this study, the stem cell "Benjamin Button" effect was seen when mice ran on a running wheel. The human equivalent of the mice exercise regime would be regular swimming, cycling, and running, a few times per week.

HACK SCORE OUT OF 10 — 🏃‍♀️🏃‍♀️🏃‍♀️🏃‍♀️🏃‍♀️🏃‍♀️🏃‍♀️ (7/10 happy runners)

Abstract: Ageing impairs tissue repair. This defect is pronounced in skeletal muscle, whose regeneration by muscle stem cells (MuSCs) is robust in young-adult animals but inefficient in older organisms. Despite this functional decline, old MuSCs are amenable to rejuvenation through strategies that improve the systemic milieu, such as heterochronic parabiosis. One such strategy, exercise, has long been appreciated for its benefits on healthspan, but its effects on aged stem-cell function in the context of tissue regeneration are incompletely understood. Here, we show that exercise in the form of voluntary wheel running accelerates muscle repair in old mice and improves old MuSC function. Through transcriptional profiling and genetic studies, we discovered that the restoration of old MuSC activation ability hinges on the restoration of Cyclin D1, whose expression declines with age in MuSCs. Pharmacologic studies revealed that Cyclin D1 maintains MuSC activation capacity by repressing TGF-β signaling. Taken together, these studies demonstrate that voluntary exercise is a practicable intervention for old MuSC rejuvenation. Furthermore, this work highlights the distinct role of Cyclin D1 in stem-cell quiescence.
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