Photo by A. MIlls, Pixnio
(Click here to listen to an audio version of this blog … Exercise and cancer )
Last week we discussed some research that explored the interactions of exercising muscles with neurons in the brain. A protein hormone, irisin, synthesized by exercising muscle cells, circulates in the body and is able to cross the blood/brain barrier. Experiments in mice have clearly shown that irisin is able to stimulate the production of new neurons in the memory center of the brain (the hippocampus) and facilitate the formation of synapses between these new neurons and existing hippocampal neurons. Further, irisin is critical to achieve exercise induced improvements in memory and learning that have been frequently documented in laboratory mice.
It turns out that an exercising muscle cell produces more chemical messengers that just irisin. A vast array of cytokines (called “myokines”) are also synthesized when a muscle cell vigorously contracts. These myokines are then released into the blood stream and target a wide range of tissues throughout the body. To date, over 600 myokines have been described, but very few have been studied sufficiently to determine their target tissues and organs in the body or their impacts.
Figure by Open Stax, Public Domain
These myokines function at variety of levels in the control of muscle and also general body homeostasis. Some are “autocrine” regulators that affect the metabolic activity of the muscle cell that synthesizes them. Some are “paracrine” regulators that influence the metabolism of cells that are near the myokine producing muscle cell. Others (like irisin) are true hormones that are “endocrine” regulators that travel via blood stream in order to influence the activity of tissues and organs that are far away from the muscle cell that synthesizes them. These distant tissues and organs include adipose tissue, the liver and, as we previously have seen in irisin, the brain.
Twenty of these myokines are produced in response to skeletal muscle contractions. These are, then, the exercise-induced myokines. A few of the better known exercise myokines are listed below (information for this discussion on these specific myokines was obtained from a January 30, 2019 review article by Jong Han Lee and Hee-Sook Jun in Frontiers in Physiology):
Myostatin is an important exercise-induced myokine that acts to inhibit the growth of the exercising muscle. While this inhibitory role may seem at first glance to be counterintuitive, bigger muscles are stronger and are often the goal of exercise programs, the role of myostatin might be better expressed as “restraining the growth” of an exercising muscle. Without this metabolic check on muscle cell proliferation and growth, muscles could grow so large and powerful that they could become less efficient in generating useful movements and even potentially damaging to the bones of the skeletal systems to which they attach.
Irisin is also a relatively well studied myokine. Its ability to change white fat over to the higher energy transducing brown fat was discussed last week as was its influence on neuron synthesis in the hippocampus of the brain. Irisin also stimulates muscle cell hypertrophy following exercise, thus acting as one of the metabolic counterforces for myostatin. Regulation of a metabolic action, like muscle growth, with opposite acting, antagonistic hormones is a common endocrine mechanism designed to gain more precise control over the ultimate homeostatic response.
Interleukin 6, Public Domain
Interleukin-6 (IL-6) is, possibly, the most well studied myokine. It has an insulin-like impact on glucose metabolism and stimulates glucose uptake and also facilitates the oxidation of high energy fatty acids in exercising muscle cells. IL-6 is associated with insulin resistance and Type-2 diabetes and obesity. It can also cause muscle atrophy.
Interleukin-15 (IL-15) acts to increase muscle mass and stimulate the use of fats for energy. It also facilitates the uptake of glucose from the blood stream and increases the endurance interval for a contracting muscle. IL-15 may behave differently in the body under different states of homeostasis and also under different methods of introduction to the blood stream. It can, in situations also cause muscle atrophy.
Myanectin (CTRP15), like IL-6 and IL-15, has an insulin-like impact on the body promoting the uptake of both blood glucose and fatty acids into exercising muscle cells.
Decorin. Figure by J. Swaminathan, Wikimedia Commons
Decorin, like irisin, is another “off-switch” for myostatin. It stimulates muscle growth.
And, finally, the very oddly, but incredibly precisely, named Secreted Protein Acidic and Rich in Cysteine (SPARC). SPARC may play a role in repairing damage to muscle cells and muscle satellite cells (“myogenic stem cells in muscle tissue”). SPARC also inhibits colon tumors by stimulating apoptosis (“programmed cell death”) in colon cancer cells.
This last myokine, SPARC, is a great segue into another very important topic concerning the potential medical benefits of exercise. Exercise has been shown in large number of epidemiological studies to both decrease the risk of getting cancer and also aid in the recovery from an established cancer. Exercise programs help cancer patients of all types recover from the effects of chemotherapy and radiation treatments and also fight back against the cancers themselves. SPARC has been shown to be a very specific, exercise-induced myokine that fights colon cancers, but many other myokines are also involved in the overall battle against cancerous tumors.
Natural Killer Cell. Photo by NIAID, Wikimedia Commons
Myokines decrease cancer cell proliferation and slow tumor growths in mice and also inhibit metastases. Myokines also stimulate the immune system to make “natural killer cells” (white blood cells that destroy tumor cells and also cells laden with viruses).
Exercise itself, over and above the production of myokines, stimulates the release of epinephrine and norepinephrine into the blood stream from the adrenal glands. These “adrenaline” hormones stimulate immune cells to enter the blood stream and also facilitates the entrance of natural killer cells into the blood. This mobilization of the immune system, with each exercise session, primes the body’s natural defenses to find and destroy tumor cells.
In serious illnesses like cancers, depression is often an accompanying and confounding condition. Exercise is well known to reduce depression although the exact mechanism of this impact is not known.
What kind of exercise are we talking about that can fight dementia and cancers and depression? Researchers have noted that both High Intensity Interval Training (HIIT) and exercise programs with longer, more moderate exercise intensities (like extended walking and biking programs) all have positive impacts on these conditions. In fact, some recent research has shown that the moderate exercise programs actually have greater impacts on regulation of body weight, blood sugar and fat metabolism.
And finally, thinking back to the blog about chronobiology and circadian rhythms ( see Signs of Winter 2, December 14, 2017): the time of day in which you exercise turns out to be very important! A study published in the journal Diabetologia in March 2021, clearly showed that participants that exercised later in the day (late afternoon to early evening) had a more effective consequential impact on their blood sugar and fat levels than those individuals who did the same exercise regime early in the morning.
Let’s all get our 150 minutes of exercise in each week! Sleep late and then work out later! Sounds like a plan to me!