How do you slow down aging? Scientists explain how exercise keeps you young

BOSTON — Time and time again, exercise continues to demonstrate its ability to protect against diseases. When it comes to aging, however, the results are not so clear cut. Now, researchers at Joslin Diabetes Center, investigating the cellular mechanism responsible for improving physical fitness through exercise, have discovered an anti-aging intervention that delayed common declines due to aging.

Exercise has been widely employed to improve quality of life and to protect against degenerative diseases, and in humans, a long-term exercise regimen reduces overall mortality,” says co-corresponding author T. Keith Blackwell, MD, PhD, a senior investigator and section head of Islet Cell and Regenerative Biology at Joslin, in a media release. “Our data identify an essential mediator of exercise responsiveness and an entry point for interventions to maintain muscle function during aging.”

This crucial mediator involves the cycle of fragmentation and repair of the mitochondria — the powerhouses of the cells. Disruption to mitochondrial health is implicated in several chronic and age-related diseases like heart disease and Type 2 diabetes.

Even worms have a hard time recovering as they age

In this study, Blackwell and the team studied the role of mitochondrial dynamics during exercise in C. elegans worms, which are commonly used in metabolic and aging research. They observed the worms as they swam or crawled to best understand age-associated decline over a 15-day period, the typical adult lifespan for this organism.

They noted a significant shift toward dysregulated mitochondria as they aged. For instance, on day one of adulthood, the team noticed fatigue and fragmentation of mitochondria after an hour of exercise within their muscle cells. However, it only took 24 hours to restore the damage.

By days five and 10, however, the worms weren’t able to bounce back within the same timeframe. Although their mitochondria went through repair processes, it wasn’t the same way as the younger animals.

“We determined that a single exercise session induces a cycle of fatigue and physical fitness recovery that is paralleled by a cycle of the mitochondrial network rebuilding,” says first author Juliane Cruz Campos, a postdoctoral fellow at Joslin Diabetes Center. “Aging dampened the extent to which this occurred and induced a parallel decline in physical fitness. That suggested that mitochondrial dynamics might be important for maintaining physical fitness and possibly for physical fitness to be enhanced by a bout of exercise.”

In another set of experiments, the team allowed the worms to swim for an hour for 10 days straight upon reaching adulthood. They found that long-term training improved their fitness by old age (day 10), which is similar to humans. Lastly, they tested well-understood interventions for exercise capacity improvement. Worms with increased AMPK — a molecule that regulates energy during exercise and supports mitochondria — showed improved physical fitness.

They also maintained capacity with aging, although it didn’t become enhanced. On the other hand, worms engineered to not have AMPK showed reduced physical fitness and impairment in mitochondrial recovery. The team hopes their findings move age-related health research in a direction that leads to greater outcomes for older adults.

“An important goal of the aging field is to identify interventions that not only extend lifespan but also enhance health and quality of life,” Blackwell concludes.

“In aging humans a decline in muscle function and exercise tolerance is a major concern that leads to substantial morbidity. Our data point towards potentially fruitful intervention points for forestalling this decline — most likely along with other aspects of aging. It will be of great interest to determine how mitochondrial network plasticity influences physical fitness along with longevity and aging-associated diseases in humans.”

The findings are published in the journal Proceedings of the National Academy of Sciences.

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