How exercise preserves physical fitness during aging: Research

Exercise may be the most powerful anti-aging intervention known to science and has been proven to protect against a wide array of diseases.

However, 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 Joslin Diabetes Center investigated the role of one cellular mechanism in improving physical fitness by exercise training and identified one anti-aging intervention that delayed the declines that occur with aging in the model organism. Together, the scientists’ findings open the door to new strategies for promoting muscle function during 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,” said co-corresponding author T. Keith Blackwell, MD, PhD, a senior investigator and section head of Islet Cell and Regenerative Biology at Joslin. “Our data identify an essential mediator of exercise responsiveness and an entry point for interventions to maintain muscle function during aging.”

That essential mediator is the cycle of fragmentation and repair of the mitochondria, the specialized structures, or organelles, inside every cell responsible for producing energy. Mitochondrial function is critical to health, and disruption of mitochondrial dynamics the cycle of repairing dysfunctional mitochondria and restoring the connectivity among 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.

“As we perceive that our muscles undergo a pattern of fatigue and restoration after an exercise session, they are undergoing this mitochondrial dynamic cycle,” said Blackwell, who is also acting section head of Immunobiology at Joslin. “In this process, muscles manage the aftermath of the metabolic demand of exercise and restore their functional capability.”

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 frequently used in metabolic and aging research.

Recording wild-type C. elegans worms as they swam or crawled, the investigators observed a typical age-related decline in physical fitness over the animals’ 15 days of adulthood. The scientists also showed a significant and progressive shift toward fragmented and/or disorganized mitochondria in aging animals. For example, they observed in young worms on day 1 of adulthood, 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 period of 24 hours was sufficient to restore both performance and mitochondrial function.

In older (day 5 and day 10) worms, the animals’ performance did not return to baseline within 24 hours. Likewise, the older animals’ mitochondria underwent a cycle of fragmentation and repair, but the network reorganization that occurred was reduced compared to that of 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,” said 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.”