Exercise may be the most effective anti-aging intervention known to science and has been shown to protect against a wide range of diseases.
While physical activity can improve health during aging, its beneficial effects inevitably decline. The cellular mechanisms underlying the relationship between exercise, fitness and aging remain poorly understood.
In a paper published in the Proceedings of the National Academy of Sciences, researchers at the Joslin Diabetes Center investigated the role of one cellular mechanism in improving physical fitness through exercise and identified one antiaging intervention that delays the declines that occur with aging in a model organism. Together, the researchers’ findings open the door to new strategies for supporting muscle function during aging.
“Exercise has been widely used to improve quality of life and protect against degenerative diseases, and in humans, a long-term exercise regimen reduces overall mortality,” said co-corresponding author T. Keith Blackwell, MD, PhD, lead researcher. and Chief of the Islet Cell and Regenerative Biology Section at Joslin. “Our data identify a critical mediator of exercise sensitivity and an entry point for interventions to maintain muscle function during aging.”
That fundamental mediator is the cycle of fragmentation and repair of mitochondria, specialized structures or organelles inside each cell responsible for energy production. Mitochondrial function is critical for health and disruption of mitochondrial dynamics, the cycle of repairing dysfunctional mitochondria and restoring connectivity between energy-producing organelles, has been linked to the development and progression of age-related chronic diseases such as heart disease. and type 2 diabetes.
“As we perceive our muscles to go through fatigue and recovery after exercise, they go through this mitochondrial dynamic cycle,” said Blackwell, who also heads the immunobiology section at Joslin. “In this process, the muscles cope with the consequences of the metabolic demands of exercise and restore their functional capacity.”
Blackwell and colleagues—including co-corresponding author Julio Cesar Batista Ferreira, PhD, Institute of Biomedical Sciences, University of Sao Paulo—investigated the role of mitochondrial dynamics during exercise in the model organism C. elegans, a simple, well-studied microscopic worm species often used in metabolism and aging research .
By recording wild C. elegans worms as they swam or crawled, the researchers observed the typical age-related decline in fitness during the animals’ 15 days of adulthood. The researchers also showed a significant and progressive shift toward fragmented and/or disorganized mitochondria in aging animals. For example, they observed a single bout of exercise-induced fatigue after one hour in young worms on day 1 of adulthood.
A 60-minute session also caused an increase in mitochondrial fragmentation in the animals’ muscle cells, but 24 hours was sufficient to restore both performance and mitochondrial function.
In older (day 5 and day 10) worms, animal performance did not return to baseline within 24 hours. Similarly, the mitochondria of older animals underwent a cycle of fragmentation and repair, but the network reorganization that occurred was limited compared to younger animals.
“We found that a single bout of exercise induces a cycle of fatigue and fitness recovery that parallels the cycle of mitochondrial network recovery,” 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 suggests that mitochondrial dynamics may be important for maintaining physical fitness and perhaps for improving physical fitness through exercise.”
In a second set of experiments, the researchers allowed wild-type worms to swim for one hour a day for 10 consecutive days, beginning at the onset of adulthood. The team found that – as in humans – a long-term training program significantly improved the fitness of the middle-aged animals on day 10 and mitigated the deterioration of mitochondrial dynamics that typically occurs during aging.
Finally, the researchers tested known life-prolonging 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 demonstrated a maintenance but not an increase in exercise performance during aging. Worms engineered to lack AMPK showed reduced fitness during aging as well as an impaired recovery cycle. They also didn’t get the age-delaying benefits of exercise during their lifetime.
“An important goal in the field of aging is to identify interventions that not only extend life but also improve health and quality of life,” said Blackwell, who is also a professor of genetics at Harvard Medical School.
Blackwell added: “In aging humans, the decline in muscle function and exercise tolerance is a major problem that leads to significant morbidity. Our data point to potentially fruitful intervention points for preventing this decline – most likely along with other aspects of aging. It will be very interesting to see how mitochondrial network plasticity influences physical fitness along with longevity and aging-related diseases in humans.”
This story was published from a wire agency source without editing. Only the title was changed.