The National Academy of Sciences investigating the role of cellular mechanisms in improving physical fitness through exercise training.
The study identified one anti-aging intervention that delayed the declines in physical fitness that occur with aging in the model organism Caenorhabditis elegans, a simple, well-studied microscopic worm species frequently used in metabolic and aging research.
The essential mediator in this process is the cycle of fragmentation and repair of the mitochondria, the specialized structures inside every cell responsible for producing energy. Mitochondrial function is critical to health, and disruption of 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.
The researchers observed a typical age-related decline in physical fitness over the worms’ 15 days of adulthood, as well as a significant and progressive shift towards fragmented and/or disorganized mitochondria in the aging worms. In young worms, a single bout of exercise induced fatigue after one hour and caused an increase in mitochondrial fragmentation in the worms’ muscle cells, but a period of 24 hours was sufficient to restore both performance and mitochondrial function. In older worms, performance did not return to baseline within 24 hours, and the network reorganization of the mitochondria was reduced compared to that of the younger worms.
To investigate the role of mitochondrial dynamics in physical fitness, the researchers targeted the protein Mfn-1, which is essential for the fusion of mitochondria. They found that targeting Mfn-1 improved the physical fitness of the worms, as well as the connectivity of the mitochondria, even in old age. These findings suggest that targeting Mfn-1 or similar proteins could be a potential strategy for maintaining muscle function during aging and improving physical fitness.
“Our data identify an essential mediator of exercise responsiveness and an entry point for interventions to maintain muscle function during aging,” said T. Keith Blackwell, MD, PhD, a senior investigator and section head of Islet Cell and Regenerative Biology at Joslin.
“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. Our findings open the door to new strategies for promoting muscle function during aging.”