Proven to protect against a wide range of diseases, exercise may be the most powerful anti-aging intervention known to science. However, although physical activity can improve health during aging, its positive effects inevitably diminish. The cellular mechanisms underlying the relationship between exercise, fitness and aging are still poorly understood.
In a paper published in Proceedings of the National Academy of Sciences, researchers at the Joslin Diabetes Center investigated the role of a cellular mechanism in improving physical fitness through exercise and identified an anti-aging intervention that delayed the declines that occur with aging in the model organism. Together, the researchers’ results open the door to new strategies to promote muscle function during aging.
“Exercise has been widely used to improve quality of life and to protect against degenerative diseases, and in humans, a long-term exercise regimen reduces overall mortality,” said corresponding author T. Keith Blackwell, MD, Ph.D., a senior investigator and Section Chief of Islet Cell and Regenerative Biology at Joslin. “Our data identify an important mediator of exercise responsiveness and a starting point for interventions to maintain muscle function during aging.”
The essential mediator is the cycle of fragmentation and repair of the mitochondria, the specialized structures or organelles, inside each cell responsible for producing energy. Mitochondrial function is critical to health, and disruption of mitochondrial dynamics—the cycle to repair dysfunctional mitochondria and restore connectivity between the energy-producing organelles—has been linked to the development and progression of chronic, age-related diseases such as heart disease and type 2 diabetes.
“When we perceive our muscles to be going through a pattern of fatigue and recovery after a workout, they’re going through this mitochondrial dynamic cycle,” said Blackwell, who is also acting section chief of immunobiology at Joslin. “In this process, muscles deal with the aftermath of the metabolic demand of exercise and restore their functional capacity.”
Blackwell and colleagues—including co-corresponding author Julio Cesar Batista Ferreira, Ph.D., Institute of Biomedical Sciences, University of Sao Paulo—examined the role of mitochondrial dynamics during exercise in the model organism C. elegans, a simple, well-studied microscopic worm species that often used in metabolism and aging research.
When the researchers recorded wild-type C. elegans worms as they swam or crawled, the researchers observed a typical age-related decline in physical fitness during the animals’ 15 days of adulthood. The researchers also showed a significant and progressive shift toward fragmented and/or disorganized mitochondria in the aging animals. For example, in young worms on day 1 of adulthood, they observed that a single bout of exercise induced fatigue after one hour. The 60-minute session also caused an increase in mitochondrial fragmentation in the animals’ muscle cells, but a 24-hour period was sufficient to restore both performance and mitochondrial function.
In aged (day 5 and day 10) worms, animal performance did not return to baseline within 24 hours. Likewise, the mitochondria of the older animals underwent a cycle of fragmentation and repair, but the network remodeling that occurred was reduced compared to that of the younger animals.
“We determined that a single bout of exercise induces a cycle of fatigue and recovery of physical fitness that parallels a cycle of mitochondrial network rebuilding,” said first author Juliane Cruz Campos, a postdoctoral fellow at the Joslin Diabetes Center. “Aging attenuated the extent to which this occurred and induced a parallel decline in physical fitness. This suggested that mitochondrial dynamics may be important for maintaining physical fitness and possibly for physical fitness to be enhanced by a bout of exercise.”
In a second set of experiments, the researchers allowed wild-type worms to swim for one hour per day for 10 consecutive days, beginning in adulthood. The team found that—as in humans—the long-term exercise program significantly improved the animals’ midlife fitness at day 10 and mitigated the decline in mitochondrial dynamics typically seen during aging.
Finally, the researchers tested known lifespan-extending interventions for their ability to improve exercise capacity during aging. Worms with increased AMPK – a molecule that is a key regulator of energy during exercise that also promotes remodeling of mitochondrial morphology and metabolism -showed improved physical fitness. They also showed maintenance of, but not improvement in, exercise performance during aging. Worms engineered to lack AMPK exhibited reduced fitness during aging as well as impaired recovery cycle. They also didn’t get the age-delaying benefits of exercise over the course of life.
“An important goal of the field of aging is to identify interventions that not only extend lifespan but also improve health and quality of life,” said Blackwell, who is also a professor of genetics at Harvard Medical School. “In aging humans, a decline in muscle function and exercise tolerance is a major problem leading to significant morbidity. Our data point to potentially fruitful points of intervention to prevent this decline—probably along with other aspects of aging. It will be of great interest to determine how mitochondrial network plasticity affects physical condition along with longevity and aging-related diseases in humans.”
Quote: Researchers highlight how exercise preserves physical fitness during aging (2023, January 5) retrieved January 5, 2023 from https://phys.org/news/2023-01-physical-aging.html
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