New study sheds light on cellular mechanisms

Elderly woman exercising

The study explored the impact of a specific cellular mechanism on improving physical fitness through exercise training. He also discovered an anti-aging intervention that could slow age-related declines in the model organism.

The results suggest potential methods for improving muscle function in the elderly.

Exercise has been shown to protect against many diseases and is considered a powerful anti-aging intervention by science. Despite its ability to improve the health of older people, its positive effects eventually diminish. The link between exercise, fitness and aging, as well as the underlying cellular mechanisms, is still not fully understood.

In an article published in the Proceedings of the National Academy of Sciences, researchers from the Joslin Diabetes Center investigated the role of a cellular mechanism in improving fitness through exercise training and identified an anti-aging intervention that delayed the declines that occur with aging in the body. model organism. Together, the scientists’ findings open the door to new strategies for promoting muscle function during aging.

“Exercise has been widely used to improve quality of life and protect against degenerative disease, and in humans, a long-term exercise regimen reduces overall mortality,” said co-corresponding author T. Keith Blackwell, MD, PhD, Principal Investigator and Section Head of Islet Cell and Regenerative Biology at Joslin. “Our data identify a critical mediator of exercise responsiveness and an entry point for interventions to maintain muscle function during aging.”

This essential mediator is the cycle of fragmentation and repair of mitochondria, the specialized structures, or organelles, inside each cell responsible for energy production. Mitochondrial function is essential 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 chronic disease. age-related, such as heart disease and type 2 diabetes.

“As we perceive that our muscles are going through a pattern of fatigue and recovery after an exercise session, they are going through this dynamic mitochondrial cycle,” said Blackwell, who is also acting section chief of immunobiology at Joslin. “In this process, the muscles manage the consequences of the metabolic demands 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 – investigated the role of mitochondrial dynamics during exercise in the model organism C. elegans, a simple, well- studied microscopic worm

In a second set of experiments, the scientists allowed wild-type worms to swim for an hour a day for 10 consecutive days, beginning in early adulthood. The team found that, as in humans, the long-term training program significantly improved the fitness of middle-aged animals by day 10 and attenuated the alteration in mitochondrial dynamics typically seen with aging.

Finally, the researchers tested known interventions that extend lifespan 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 better fitness. They have also demonstrated the maintenance, but not the improvement, of physical performance during aging. Worms engineered to lack AMPK exhibited reduced fitness during aging as well as impaired recovery cycle. They also did not experience the age-delaying benefits of exercise in their lifetime.

“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, decline in muscle function and exercise tolerance is a major concern that leads to significant morbidity. Our data point to potentially fruitful points of intervention to prevent this decline – most likely with d other aspects of aging It will be of great interest to determine how the plasticity of the mitochondrial network influences fitness as well as longevity and diseases associated with aging in humans.

Reference: “Exercise Preserves Fitness During Aging Through AMPK and Mitochondrial Dynamics” by Juliane Cruz Campos, Luiz Henry Marchesi Bozi, Barbara Krum, Luiz Robert Grassmann Bechara, Nicholas Dresch Ferreira, Gabriel Santos Arini, Ruda Prestes Albuquerque, Annika Traa, Takafumi Ogawa, Alexander M. van der Bliek, Afshin Beheshti, Edward T. Chouchani, Jeremy M. Van Raamsdonk, T. Keith Blackwell and Julio Cesar Batista Ferreira, January 3, 2023, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2204750120

This work was supported by the Fundação de Amparo at Pesquisa do Estado de São Paulo (FAPESP); National Research and Development Council – Brazil (CNPq); Coordination for the Improvement of Higher Education Personnel – Brazil (CAPES) Finance Code 001 and National Institute of Science and Technology and Center for Research and Development of Redox Processes in Biomedicine; National Institutes of Health (NIH); the Joslin Diabetes Center; FAPESP postdoctoral fellowships; the American Heart Association Career Development Award; the Claudia Adams Barr program; the Lavine Family Fund; the Pew Charitable Trust. William B. Mair (Harvard TH Chan School of Public Health) and Malene Hansen (Sanford Burnham Prebys Medical Discovery Institute) provided some of the worm strains used in this study. Other strains were provided by the CGC, which is funded by the NIH.

Chouchani is founder and shareholder of Matchpoint Therapeutics. The other authors declare no competing interests.

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