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While the exercised mice scampered and scurried about their cages, the aging non-runners huddled in a corner, barely moving.” Sharon Kirkey, Montreal Gazette (February 22, 2011)
“We know that exercise has benefits even when humans start over the age of 65. But this study clearly shows that we can get closer to the Fountain of Youth if we start when we’re young and do moderate exercise our whole life.” Mark Tarnopolsky, professor of pediatrics and medicine, McMaster University, Canada
Exercise Proves Amazing Rejuvenator
Running Mice Remain Youthful While Sedentary Siblings Dying
Exercise is the closest thing we’re likely to find to the proverbial Fountain of Youth. Ask Mark Tarnopolsky, professor of pediatrics and medicine at Canada’s McMaster University. He put fast-aging mice on a running program—with phenomenal results. Exercise rejuvenated virtually every tissue and organ in their bodies, including mitochondria, muscle mass, brain, heart, and gonads.
Tarnopolsky’s study is grounded in the mitochondrial theory of aging. The mice used were ideally suited to test the hypothesis—and the power of exercise.
As noted in our recent piece profiling master athlete phenoms Olga and Ed, researchers are increasingly seeing aging as a mitochondrial disease. Defective mitochondria appear as we get older, robbing us of endurance, strength and function. Mitochondria combine oxygen and nutrients to create fuel for nearly every cell in the body. When mitochondria go bad, cells all over the body begin to wither and die.
Tarnopolsky and colleagues used mice lacking the primary mitochondria repair mechanism, which caused them to begin aging rapidly at about three months, the human equivalent of 20 years. By the time they reached eight months (60 for humans), they were old, inside and out. All were dead before reaching one year. All, that is, but the runners.
The mice were genetically engineered to age rapidly due to defective mitochondrial polymerase gamma (PolG), which disrupts the repair of mitochondria. The engineered animals, called PolG Mice, had previously provided the “first direct cause-and-effect evidence” that dysfunctional mitochondria result in premature aging and related pathologies, Tarnopolsky and colleagues explained in their report.
Mitochondria are unique in that they have their own DNA. Accumulated damage to the mitochondrial DNA leads to an energy crisis which results in a progressive decline in tissue and organ function. Without a repair mechanism, these mice were targeted for premature aging. Tarnopolsky's sedentary mice deteriorated as expected, but not to their fellow mutants that began running at three months.
The mice ran on a wheel for 45 minutes three times a week, at about 15 minutes per mile. “It was about like a person running a 50- or 55-minute 10K,” principal investigator Tarnopolsky related. (10K is 6.2 miles.) The mice continued running for five months.
The mice that ran remained youthful and healthy, while their sedentary peers were balding, graying, shrinking, and losing interest in the opposite sex. The runners had full pelts and no graying. They maintained their muscle mass and brain volume. Their gonads and ovaries were normal, along with their hearts.
“Not only did the treadmill-running mice look as sleek-coated, bright-eyed, and bushy-tailed as wild mice, but the researchers also saw huge recovery in age-related damage to practically every tissue they could analyze,” The Montreal Gazette reported. (The runners were actually more fit than wild mice.)
“Every part of the body was protected by exercise,” Tarnopolsky reported enthusiastically. “I think that exercise is the most potent anti-aging therapy available today or likely forever.”
It’s not clear just how exercise changed the aging process of these mice. What is clear is that exercise stimulated mitochondria by some mechanism outside the normal pathway, which didn’t exist for these mutant mice.
The researchers offered several theories. One is that exercise promoted regeneration of healthy mitochondria not affected by defective polymerase. In addition, they speculated that that endurance exercise stimulated release of metabolites that “may promote organ cross-talk, resulting in systemic mitochondrial biogenesis and multisystem rejuvenation. These adaptations may…[dilute] the pathological effects of mitochondrial DNA point mutations incurred systemically in PolG mice.”
Dr. Tarnopolsky is currently overseeing experiments to uncover the precise mechanisms involved. But for now, he says, the lesson of this experiment and many others like it is unambiguous: “Exercise alters the course of aging.”
“Others have tried to treat these animals with exercise pill drugs and have even tried to reduce their caloric intake, a strategy felt to be most effective for slowing aging, and those were met with limited success,” Tarnopolsky related.
Adeel Safdar, lead author and senior PhD student working with Tarnopolsky said, “I believe we have very compelling evidence that clearly show that endurance exercise is a lifestyle approach that improves whole body mitochondrial function which is critical for reducing morbidity and mortality. Exercise truly is the Fountain of Youth.”
Co-author Jacqueline Bourgeois summarized: “The recipe for healthy aging is very simple, and that’s exercise.” Bourgeois is an associate professor of pathology and molecular medicine at McMaster University.
“Our data clearly support endurance exercise as a medicine and a lifestyle approach to improving systemic mitochondrial function, which is critical for reducing morbidity and mortality across the lifespan,” the research team wrote in their report.
Take Home Messages
While many were impressed that the active mice kept their hair, it may take more to move the younger crowd. Dr. Tarnopolsky confided to New York Times writer Gretchen Reynolds that his younger graduate students were most interested in the animal’s robust gonads. “I think they all exercise now,” he said.
Adding a more serious note, Tarnopolsky told The Montreal Gazette: “We know that exercise has benefits even when humans start over the age of 65. But this study clearly shows that we can get closer to the Fountain of Youth if we start when we’re young and do moderate exercise our whole life.”
Importantly, Dr. Tarnopolsky told The New York Times that aerobic exercise is not the only form of exercise that alters aging. Studies of older humans have shown that weightlifting can also improve mitochondrial health, he noted to Gretchen Reynolds. (See also http://www.cbass.com/AerobicsNeedIt.htm )
If you haven’t been exercising, walking is a good place to start. “Anything is better than nothing,” Tarnopolsky counseled.
(The Tarnopolsky study was published on February 21, 2011, in the journal Proceedings of the National Academy of Sciences.)
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