While we’re all at home and practicing social distancing during this global pandemic, it has become a challenge to get in daily exercise. Aside from outward physical appearance, what other benefits does exercise hold? Dr. Thomas Rando and his team at Stanford University explored this question in more detail in a CIRM supported animal study.
The Stanford research team found that exercise played a key role in restoring the youthful properties in the muscle stem cells of old mice. Muscle stem cells play an important role in tissue regeneration. They are usually on standby alongside muscle fibers in a resting state known as quiescence until called upon to repair damage.
For this study, the researchers wanted to see if voluntary exercise had an effect on the muscle stem cells in mice. Older mice that were 20 months old, the equivalent of 60-70 human years, were given an exercise wheel where they were allowed to run at will. Younger mice that were 3-4 months old, the equivalent of 20-30 human years, were also given an exercise wheel and allowed to run at will. A separate group of younger and older mice were given a wheel that didn’t rotate to compare them with the groups of mice that exercised.
They found that the older animals that had exercised regularly were significantly better at repairing muscle damage compared to their counterparts that did not exercise. However, this exercise benefit was not observed between the younger group of mice.
The researchers also transplanted the muscle stem cells from the older mice that had exercised into younger mice that had not exercised. They found that the muscle stem cells from the older mice contributed more to the repair process than did those from the non-exercising mice.
What was also surprising is that injecting blood from an old mouse that had exercised into an old mouse that hadn’t created a similar benefit in the muscle stem cells. This finding suggests that exercise simulates the production of some factors that then circulate in the blood and enhance the function of older stem cells.
Lastly, the researchers were ably to identify a molecular pathway that activates the resting muscle stem cells in response to damage.
In a press release, Dr. Rando discusses how this discovery could potentially lead to the development of a drug that could rejuvenate muscle stem cells.
“If we could develop a drug that mimics this effect, we may be able to experience the benefit without having to do months of exercise.”
The full results of this study were published in Nature Metabolism.
The Stem Cellar 
All cells require oxygen to survive strongly and healthy. Cell lack of oxygen tend to become anergy and eventually lead to apotosis. Children and adults have normal range of heart beat, 60-100bpm. However, the heart rate declines accordingly with ages because older hearts simply do not beat as fast as younger hearts. As people age increase, the older hearts tend to enlarge slightly to develop thicker wall and slightly larger chamber. This result is mainly due to an increase in size of individual heart muscle cells. The development of stiffiness heart walls in older hearts cause the left ventricle does not functioning effectively and lead to heart failure. This is coupling with the walls of the arteries and arterioles become thicker, less elastic, stiffer and less resilient. The consequences of negative impacts in olders may cause their blood circulation obstructed and distribution of oxygen in blood is not delivered evenly to all the cells. Therefore, the cells become hypoxic and unhealthy. However, this deteriorate effects can be overcome by regular exercise to maintain the fitness of cardiovascular and muscular. This evidence strongly support the indication that muscular stem cells of older animals exercised regularly were significantly better at repairing muscle damage compare to their counterparts that did not exercise.
The development of organs and tissues in youngs are not significantly affected by exercising. Thus, the benefit of exercise was not observed between the younger group of mice.
Stem cells of old people have gone through many times of cell division and life cycles of growth hormones and growth factors regulation during their entire lives time. The system of signalling network in older stem cells can be more developed and the cells become more sensitive to the influence of growth factors in the environmental. Therefore, the transplanted muscle stem cells from the older mice that had exercised into younger mice without exercised showed muscle stem cells of older mice can speed up the process of repairing than non-exercised mice.
Cyclin D1 is a protein required to drive the cell cycle from resting stage of G1 to progress into transition phase of G1/S for the beginning of proliferation. Cyclin D1 is sensitive to the extracellular signal triggering for proliferation of cell. The expression levels of cyclin D1 is highly response to the signal of proliferative including growth factor receptors, Ras and downstream efectors. Therefore, the healthy cells of older mice with regular exercised produced more cyclin D1 in blood in response to the need of proliferation in their bodies. Thus, the experiment study by injecting the blood from an old mouse with exercised into an old mouse without exercised produced a similar benefit in the growth of mouse stem cells.
Do I understand correctly: blood from an exercising mouse gives benefit if transfused into the body of a non-exercising mouse? That sounds hugely significant in the fight against heart disease. Is this a CIRM-funded project? Who could I talk to about this?
Hi Don, you understand correctly. Here’s a link to the Stanford News article about the research. It gives the researcher’s name and mentions our support for this work at the bottom: https://med.stanford.edu/news/all-news/2020/04/exercise-restores-youthful-properties-to-muscle-stem-cells-of-ol.html