PNAS: A cellular mechanism for improving physical fitness through exercise training

Exercise has been shown to prevent a wide range of diseases and may be the most effective anti-aging intervention
known to the scientific community.
However, while physical activity can improve health during aging, its beneficial effects inevitably decline.

The cellular mechanisms underlying the relationship between exercise, health, and aging are still poorly
understood.

In a paper published in the Proceedings of the National Academy of Sciences, researchers at the Jocelyn Diabetes Center studied the role of a cellular mechanism in improving physical health through exercise training and identified an anti-aging intervention that could delay the decline
that occurs with aging in model organisms.
In conclusion, the scientists' findings open the door
to new strategies to boost muscle function during aging.

"Exercise is widely used to improve quality of life and prevent degenerative diseases, and in humans, long-term exercise regimens can reduce overall mortality," said co-corresponding author T.
Smith.
Keith Blackwell, MD, said, "Our data identify an important mediator of exercise responsiveness and an entry point for interventions that maintain muscle function during aging
.
”

This important intermediary is the cycle of division and repair of mitochondria, specialized structures or organelles
within each cell responsible for producing energy.
Mitochondrial function is essential for health, and disruption of mitochondrial dynamics (cycles that repair dysfunctional mitochondria and restore connectivity between energy-producing organelles) has been linked to the onset and progression of chronic age-related diseases such as heart disease and type 2 diabetes
.

"We found that our muscles go through a pattern of fatigue and recovery after exercise, and they are going through this mitochondrial dynamic cycle, in which muscles manage the consequences of the metabolic demands of exercise and restore their functional capacity
.
"

Blackwell and his colleagues – including co-corresponding author Julio Cesar Batista Ferreira, Ph.
D.
, Institute of Biomedical Sciences, University of São Paulo – studied the role of mitochondrial dynamics in motility in the model organism C.
elegans, a simple, well-studied microscopic worm species often used in metabolic and aging studies
.

The researchers recorded wild-type Caenorhabditis elegans swimming or crawling, observing typical age-related declines in the animals' physical health within 15 days of reaching
adulthood.
The scientists also showed that in aging animals, mitochondria showed a clear, gradual fragmentation and/or disordered transition
.
For example, they observed that young nematodes on the first day of adulthood can cause fatigue
after an hour of exercise.
60 minutes of exercise also led to an increase in mitochondrial debris in animal muscle cells, but 24 hours was sufficient time to restore motor performance and mitochondrial function
.

In older nematodes (days 5 and 10), the animal's performance did not return to baseline
within 24 h.
Similarly, the mitochondria of older animals undergo a cycle of division and repair, but less recombination occurs compared to younger animals
.

"We determined that a single exercise can induce cycles of fatigue and physical recovery, parallel
to cycles of mitochondrial network reconstruction.
Aging inhibits the occurrence of this condition and leads to a parallel decline
in physical fitness.
This suggests that mitochondrial dynamics may be important for maintaining good health, and may also be important
for enhancing physical fitness through exercise.
”

In the second set of experiments, scientists had wild-type nematodes swim for an hour a day for 10 days
, starting as adults.
The team found that, like in humans, a long-term training program significantly improved the animals' midlife health on day 10 and alleviated mitochondrial dynamic damage
common during aging.

Finally, the researchers tested the ability
of known life-extending interventions to improve exercise capacity during aging.
AMPK, a key regulator of energy during exercise, also promotes the remodeling of mitochondrial morphology and metabolism, and worms with increased AMPK show better physical fitness
.
They have also been shown to maintain, rather than enhance, athletic performance
during aging.
Worms designed to lack AMPK show decreased physical fitness as well as impaired
recovery cycles during aging.
They also don't get the benefits
of slowing aging from exercise during their lifetime.

"An important goal in the field of aging is to identify interventions that not only prolong life, but also improve health and quality of life, and in older adults, decreased muscle function and exercise tolerance are major problems
leading to a large number of morbidity.
Our data point to potentially effective interventions to prevent this decline – likely along with
other aspects of aging.
It would be very interesting
to determine how the plasticity of mitochondrial networks affects physical health in humans as well as longevity and aging-related diseases.
”