Maybe have another cup of coffee?

Running and caffeine work together against skin cancer in mice

Exercise and caffeine work together to eradicate skin cancer, researchers say. Mice that combine the stimulating caffeine with daily running manage to fight against the cellular damage caused by ultraviolet light better than animals that only practice running or only drink highly caffeinated water.

"We think that caffeine contributes much more than physical exercise alone," says Alan Cooney, a biologist at Rutgers University in New Jersey, who led the study recently published in the journal PNAS.

Skin cancer that is triggered by exposure to the sun, such as squamous cell carcinoma, is one of the most common types of cancer in the US, and is responsible for more than a million cases a year!

One or two cups

Previous studies in mice have shown that drinking caffeinated tea reduces the number of skin tumors, and that jogging after exposure to ultraviolet light stimulates the process of programmed cell death, thus protecting the body from skin cancer. In both studies, the mice tested had less subcutaneous fat than mice that did not receive these treatments, suggesting a link between cancer and body fat.

To test whether these tendencies hold for both caffeine and exercise, Connie's research group gave hairless mice caffeinated water and access to a running wheel. Parallel systems of mice received either caffeine only, or running wheel only, or neither.

Both the mice on caffeine and a running wheel and the mice that were not stimulated by caffeine but received running wheels ran approximately 3.5 kilometers per day. "It's much more than a walk in the park" says Connie.

After two weeks, the researchers exposed the mice to ultraviolet light, which causes sunburn and DNA damage that may lead to the development of skin cancer.

The skin cells of mice that both exercised and drank caffeine showed the highest levels of programmed cell death, a phenomenon known as apoptosis, in which damaged cells "suicide" and thus prevent the dangerous accumulation of defects that could manifest in the form of cancer. These mice also had more cells with two key proteins, which play a significant role in the process of apoptosis - the proteins caspase-3 and phospho-p53.

In this study, the effect of a higher caffeine level was also tested. It turned out that excess caffeine does not necessarily lead to less cancer. The athletic mice in the study who drank the human equivalent of 3-5 cups of coffee per day had fewer apoptotic cells compared to the athletic mice who drank the human equivalent of 1-2 cups of coffee per day.

Together, the caffeine and exercise helped the mice lose more fat than mice that received the other treatments. On average, the weight of the mice was the same, but the caffeine runners had less subcutaneous fat. Connie thinks that the adipose tissue may also secrete molecules that may promote cancer. Surgical removal of fat, as reported in the article Stay trim to cut cancer risk, stimulates apoptosis in sunburned skin cells.

The connection to cancer

It's too early to determine whether humans should be jumping double expressos in the back and evening while sprinting on the treadmill at the gym, all following the findings of the study presented here, says Hasan Mukhtar, a skin cancer expert at the University of Wisconsin-Madison. According to him, it remains to be checked how the information obtained from mice is translated back to human patients, but the basic idea is good and it should be continued to be checked.

Several epidemiological studies have linked caffeine or physical exercise to a decrease in the incidence of skin, liver and breast cancer. "We have to carefully conduct studies on humans," says Connie, a two-cup-of-coffee-a-day drinker and occasional athlete. "I try to exercise. Do I enjoy it? I'm not so sure.”

More information about apoptosis, from the article "Chronicle of pre-planned death" published in the journal Galileo, by Naomi Ashchar:
Every cell in our body has a "suicide" mechanism (apoptosis). This mechanism takes part in the most vital processes. The proper functioning of multicellular organisms, including that of humans, depends not only on the ability of the body to produce new cells at any time, but also on its ability to destroy certain cells in a pre-planned manner. This self-destruction command occurs when the cell is redundant and no longer brings any benefit, when it is produced in too much and creates a disorder that can develop into a cancerous growth, or in a situation where it carries damage and genetic defects and develops poorly, and even then may develop into a cancerous growth.

Programmed cell death is associated with genetic and acquired diseases. One of the diseases is cancer. When there is a delay in the planned cell death process as a result of a deficiency in its control, there is a decrease in the number of cells that commit suicide and cancerous tumors develop. Chronic inflammatory diseases (such as shortness of breath and atherosclerosis) and autoimmune diseases, in which the body's immune system destroys its own tissues (such as rheumatoid arthritis), are also associated with apoptotic processes. Deficiencies in the control of the suicide process, which cause it to accelerate and increase the number of suicidal cells, contribute to the development and worsening of degenerative diseases of nerve cells in the brain (in Alzheimer's and Parkinson's diseases for example); for acquired immunodeficiency (AIDS); For stroke and heart attacks and in certain cases of kidney and liver damage.

Not all cell death in the body is done by the process of apoptosis; Cell death can also occur in the process of necrosis. In necrosis, the cell is a passive victim - it is damaged by changes that occur in it or in its environment, for example a lack of oxygen. Through microscopic observations it is possible to distinguish between cells that die following programmed death and cells that die from necrosis. Necrotic damage prevents the cell from balancing its fluid balance and osmotic equilibrium. In this situation, water and ions penetrate into the cell, damaging vital organelles, and the cell inflates like a balloon. Cell death as a result of necrosis is an inflammatory process, and at the end cells of the immune system engulf the damaged cell - an action that may harm healthy cells located nearby.

Unlike necrosis, in the process of planned death the cell is an active victim that wastes energy for the purpose of its elimination. The cell does not swell, but actually shrinks, and detaches from the neighboring cells. During apoptosis, the cell is in a kind of "boiling" state: vesicles appear and bubble on its surface, sometimes they disappear and new vesicles appear in their place. The internal organelles of the cell maintain their shape, with the exception of the nucleus - it changes dramatically. The most noticeable change occurs in DNA and nuclear proteins. They are compressed together into bubbles near the nuclear envelope. At this stage the dying cell is engulfed by nearby cells or by "scavengers" cells that wander through the tissues. Planned death is not accompanied by an inflammatory process, and the killing process is carried out in a very clean way - the dying cells are quickly swallowed even before toxic decomposition products are formed. Sometimes the apoptotic cells undergo additional changes before they are swallowed: the cell nucleus is detached, and the cell itself divides into several bodies that contain nuclear particles, they are also removed by the "garbage collectors".

The timing at which cell suicide occurs, the signals that trigger it and the execution process, all of these are being vigorously investigated today by many research groups around the world. It is common to distinguish the cell suicide process in three stages: the initiation stage, the "judgment" stage or making the decision, and the execution stage.

The arousal phase: There are many different factors that "pull the trigger" - those that trigger the killing mechanism. Among them are factors that cause damage to the cell, such as ionizing radiation, infection with viruses, lack of growth factors and the presence or lack of various hormones. These factors can act inside or outside the cell. They activate mediator proteins that are responsible for transmitting the apoptotic message.

The judgment phase: The decision to "suicide" is made using unique substances responsible for transmitting the apoptotic message, which activate suicide receptors in the cells. These substances can trigger suicide as well as prevent it.

The execution phase: the apoptotic message goes to special proteins that execute the self-destruction. Included in them is a special family of enzymes that are produced in every cell and are called caspases. Ten such enzymes are known today. They can be described as sharp knives stored in their sheaths in a resting state. When a cell functions properly and benefits the body, the suicide process is paralyzed, and the cell does not allow these "knife enzymes" to work. But when the cell is attacked by a pollutant or becomes malignant and endangers the body, those deadly proteins are pulled out of their slumber and begin to crush the other cell proteins; The cell's infrastructure is destroyed and with it the hereditary material is also damaged, and the cell becomes extinct. Recently, additional proteins belonging to this group of enzymes have been identified in mammals.

Adaptation of an article from Nature