Exercise, which has been proven to protect against a variety of diseases, may be the most powerful anti-aging intervention known to science. Yes, but its beneficial effects are inevitably diminished. 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 Joslyn Diabetes Center have investigated the role of one cellular mechanism in improving physical fitness with exercise training and identified one anti-aging intervention that slows age-associated decline in model organisms. findings open the door to new strategies for promoting muscle function during aging.
“Exercise has been widely adopted to improve quality of life and protect against degenerative diseases, and in humans, long-term exercise regimens reduce overall mortality,” said co-corresponding author and senior investigator. said T. Keith Blackwell, M.D., Ph.D. Joslin’s Head of Islet Cell and Regenerative Biology. “Our data identify key mediators of exercise response and starting points for interventions to preserve muscle function during aging.”
Its key mediator is the cycle of fragmentation and repair of mitochondria, specialized structures, or organelles in every cell that produces energy. A cycle that repairs dysfunctional mitochondria and restores connections between energy-producing organelles. It is associated with the development and progression of age-related chronic diseases such as heart disease and his type 2 diabetes.
“Our muscles experience this mitochondrial dynamic cycle because they perceive themselves to be experiencing patterns of fatigue and recovery after an exercise session,” says Joslin’s head of immunobiology. said Blackwell, who is also “In this process, the muscle manages the aftermath of metabolic demand from exercise and restores functional capacity.”
Blackwell and colleagues – including co-lead author Julio Cesar Batista Ferreira, Ph.D., Institute of Biomedical Sciences, University of São Paulo. We investigated the role of mitochondrial dynamics during locomotion in the model organism C. elegans. Nematodes are a simple, well-studied microscopic worm species frequently used in metabolic and aging studies.
Researchers who documented swimming and crawling in wild-type worms observed a typical age-related decline in strength over the 15 days after the animals reached adulthood. Scientists have also shown significant and gradual changes toward fragmented and/or disorganized mitochondria in aging animals. For example, they observed that in a young nematode on his first day of adulthood, one exercise induced fatigue in him one hour later. A 60-minute session also increased mitochondrial fragmentation in the animal’s muscle cells, but 24 hours was enough for him to restore both performance and mitochondrial function.
In older (days 5 and 10) worms, animal performance did not return to baseline within 24 hours. Similarly, mitochondria in older animals underwent cycles of fragmentation and repair, but the network reorganization that occurred was reduced compared to younger animals.
We determined that a single exercise session induced cycles of fatigue and recovery of strength in parallel with cycles of remodeling of the mitochondrial network. Aging attenuated the extent to which this occurred and at the same time caused a decline in physical fitness. doing.”
Juliane Cruz Campos, First Author, Postdoctoral Fellow, Joslin Diabetes Center
In a second set of experiments, scientists allowed wild-type worms to swim for 1 hour a day for 10 consecutive days from the onset of adulthood. The team found that — just like humans — a long-term training program significantly improved fitness in middle-aged animals on day 10, counteracting the impairments in mitochondrial dynamics normally seen during aging. Reduced.
Finally, researchers tested known interventions that extend lifespan for their ability to improve exercise performance during aging.Worms with increased AMPK-; Molecules that also promote morphological and metabolic remodeling–showing increased physical fitness. It also showed maintenance of exercise performance with aging, but not enhancement. Worms engineered to lack AMPK showed age-related decline in physical fitness and impaired recovery cycles. They also did not enjoy the aging-slowing effects of exercise over their lifetimes.
“An important goal in the aging field 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, decreased muscle function and exercise tolerance are major concerns, leading to substantial morbidity. Our data, like other aspects of aging, anticipate this decline. It points to a potentially beneficial intervention point for human health, which is great.There is interest in figuring out how mitochondrial network plasticity affects physical fitness along with human longevity and age-related diseases. I have.”
Additional authors include Takafumi Ogawa of Joslyn Diabetes Center. Luiz Henrique Marchesi Bozi (co-first author) and Edward Chouchani of the Dana-Farber Cancer Institute. Barbara Krum, Luiz Roberto Grassmann Bechara, Nikolas Dresch Ferreira, Gabriel Santos Arini, and Rudá Prestes Albuquerque from the University of São Paulo. Annika Traa of McGill University. Alexander M. van der Bliek of the David Geffen School of Medicine, University of California, Los Angeles. Afshin Beheshti of NASA Ames Research Center. and Jeremy M. Van Raamsdonk of Harvard Medical School.
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Journal reference:
Campos, JC, and others. (2023) Exercise maintains fitness during aging through AMPK and mitochondrial dynamics. PNAS. doi.org/10.1073/pnas.2204750120.
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