The outcomes counsel potential strategies for enhancing muscle perform in older adults.
Train has been demonstrated to protect in opposition to quite a few illnesses and is taken into account a potent anti-aging intervention by science. Regardless of its capability to boost well being in older people, its constructive results finally diminish. The connection between train, health, and growing old, in addition to the underlying mobile mechanisms, continues to be not absolutely understood.
In a paper revealed within the Proceedings of the Nationwide Academy of Sciences, researchers at Joslin Diabetes Heart investigated the function of 1 mobile mechanism in enhancing bodily health by train coaching and recognized one anti-aging intervention that delayed the declines that happen with growing old within the mannequin organism. Collectively, the scientists’ findings open the door to new methods for selling muscle perform throughout growing old.
“Train has been extensively employed to enhance high quality of life and to guard in opposition to degenerative illnesses, and in people, a long-term train routine reduces total mortality,” mentioned co-corresponding writer T. Keith Blackwell, MD, PhD, a senior investigator and part head of Islet Cell and Regenerative Biology at Joslin. “Our information establish a vital mediator of train responsiveness and an entry level for interventions to take care of muscle perform throughout growing old.”
That important mediator is the cycle of fragmentation and restore of the mitochondria, the specialised constructions, or organelles, inside each cell chargeable for producing power. Mitochondrial perform is crucial to well being, and disruption of mitochondrial dynamics the cycle of repairing dysfunctional mitochondria and restoring the connectivity among the many energy-producing organelles — has been linked to the event and development of persistent, age-related illnesses, equivalent to coronary heart illness and sort 2 diabetes.
“As we understand that our muscle groups endure a sample of fatigue and restoration after an train session, they’re present process this mitochondrial dynamic cycle,” mentioned Blackwell, who can be performing part head of Immunobiology at Joslin. “On this course of, muscle groups handle the aftermath of the metabolic demand of train and restore their useful functionality.”
Blackwell and colleagues — together with co-corresponding writer Julio Cesar Batista Ferreira, Ph.D., Institute of Biomedical Sciences, College of Sao Paulo — investigated the function of mitochondrial dynamics throughout train within the mannequin organism C. elegans, a easy, 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 the 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.”
In a second set of experiments, the scientists allowed wild-type worms to swim for one hour per day for 10 consecutive days, starting at the onset of adulthood. The team found that — as in people — the long-term training program significantly improved the animals’ middle-aged fitness at day 10, and mitigated the impairment of mitochondrial dynamics typically seen during aging.
Finally, the researchers tested known, lifespan-extending 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 which also promotes the remodeling of mitochondrial morphology and metabolism — exhibited improved physical fitness. They also demonstrated maintenance of, but not enhancement of, exercise performance during aging. Worms engineered to lack AMPK exhibited reduced physical fitness during aging as well as impairment of the recovery cycle. They also did not receive the age-delaying benefits of exercise over the course of the lifespan.
“An important goal of the aging field is to identify interventions that not only extend lifespan but also enhance health and quality of life,” said Blackwell, who is also a professor of genetics at Harvard Medical School. “In aging humans, a decline in muscle function and exercise tolerance is a major concern that leads to substantial morbidity. Our data point towards potentially fruitful intervention points for forestalling this decline — most likely along with other aspects of aging. It will be of great interest to determine how mitochondrial network plasticity influences physical fitness along with longevity and aging-associated diseases in humans.”
Reference: “Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics” by Juliane Cruz Campos, Luiz Henrique Marchesi Bozi, Barbara Krum, Luiz Roberto Grassmann Bechara, Nikolas Dresch Ferreira, Gabriel Santos Arini, Rudá 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, 3 January 2023, Proceedings of the National Academy of Sciences.
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Pesquisa e Desenvolvimento – Brasil (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) Finance Code 001 and Instituto Nacional de Ciência e Tecnologia and Centro de Pesquisa e Desenvolvimento de Processos Redox em Biomedicina; 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 T.H. 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 a founder and equity holder in Matchpoint Therapeutics. The other authors declare no competing interests.