We all know someone who has been through the traumatic and sadly often fatal ordeal of a cancer diagnosis and subsequent treatment. The UK has made strides to inform the population to the common risk factors for cancer and the benefits of exercise. They roll off the top of your head as easily as your home address or your number. However, we also choose to ignore the advice that successive government health campaigns and even the education system itself has taught us over the years.
This article aims to elucidate the effects of exercise on cancer genesis and progression.
Exercise has profoundly positive effect on our immune system and the effect is almost instantaneous. The immune system is our body’s way of fighting off foreign cells such as viruses or bacteria, it plays a part in inflammation and importantly it also has a role in tumour suppression and prevention.
The evidence for the role of exercise on the immune response was first discovered in 1893. It first described how leukocytes (white cells) increased in the bloodstream during physical exertion. The link between exercise and activation of the immune system had now been observed.
The focus of recent studies in the field has been on a specific type of white blood cell (WBC) called a ‘natural Killer’ cell (NK cell) NK cells are produced in the bone marrow from CD34+ precursor cells and are part of the innate immune system and respond rapidly to threats in the body. NK cells are stored in the spleen and the vascular bed and during exercise, both of these organs have their blood flow increased significantly, and also increases their numbers in circulatory system.
NK cells have a ‘natural’ ability to seek and destroy premalignant and malignant cells without the need to first be exposed to the cell in order to develop a defence (adaptive immunity) However, they do play a major part in training the adaptive immune system.
Credit: Trends in Molecular Medicine.
Research has suggested that NK recruitment into the bloodstream can increase six fold in as little as 70 seconds of physical activity. Whereas, other studies have shown that NK increases in the bloodstream can be produced within minutes of exercise taking place. This is also in agreement with other studies that have investigated the role of exercise and white cells. However, following 30mins of endurance exercise, NK cell numbers did not increase. The general consensus in the literature is that the exercise intensity to elicit an increase in NK numbers must be sufficient for an increased heart rate and breathlessness to occur. Moderate to high intensity endurance and resistance type activities. However, exercise beyond 3 hours results in a decrease in circulating NK cells.
Research supports evidence for the benefits of exercise that we can all relate to. Overtraining can cause harm and lead to opportunistic infections that would have otherwise been dealt with by the immune system. A possible example of this is the middle distance runner Sebastian Coe and the American sprinter Carl Lewis. Two such examples of how over training may have been detrimental to success. Seb Coe failed to qualify for the 1988 Seoul Olympics due to a respiratory illness whilst Carl Lewis failed to qualify for the 1992 Olympic 100m due to an infection. While the evidence linking over training to their respective failure to qualify is not sufficient for a definitive answer. The circumstantial evidence would certainly point in that direction.
The two different subtypes of NK cells that are activated during and post exercise are known as CD56dim and CD16+ compared to all other NK cell subtypes. CD56dim and CD16+ cells are more cytotoxic (cell destroying) than other subtypes which are said to be more cytokine (molecular signalling) producing NK cells.
Cytokines are the messengers of the immune system. They are produced in certain WBC’s in order to ‘communicate’ or signal other cells of the immune system. Exercise releases myokines from the muscle fibres into the circulation. Myokines are proteins released by the muscle during contractions. The myokines are signalling molecules that activate the NK cells. Interleukin 6, 7 and 15 (IL 6, IL7 & IL15) have been seen to play a role in NK cell activation during exercise. Furthermore, epinephrine release pre and during exercise is also thought to recruit NK cells into the circulatory system.
Cytokine Map: This image shows you the different cytokines and their functions.
The role of exercise intensity, mode and duration of exercise and the various signalling pathways that activate the tumour fighting NK cells is now a bit more transparent. This could help fitness professionals to widen the scope of exercise.
The increasing body of research that has examined the effects of exercise and aging on cancer and the immune system. The general consensus is that exercise still has the same positive effect on reducing the risk of malignancies developing.
The ageing process is a complex topic involving many different variables that all contribute to the process. However, in essence, the ageing process can be thought of as an accumulation of cellular damage over time. This can be from free radical exposure and oxidative stress on cells leading to in effect cellular exhaustion. Therefore, leading to cellular dysfunction. However, the already established immediate responses of NK cells to exercise is supported by research that also suggests that elderly populations who undergo a 12 week aerobic and resistance training programme display increased antigen expression on monocytes (immune cell), decreased inflammation and inhibit a tumour promoting environment whilst promoting a tumour suppressive one.
There are studies that explore the immune response to exercise in people who have been diagnosed with cancer. The findings are in agreement with research looking into non cancer patients. The same NK cell response is seen in healthy populations and in control groups or people with malignancies. However, there is still a great deal to be done to find out if the immune response seen in both populations has any beneficial effect on clinical outcomes.
Exercise has a profound effect on blood flow around the body. Blood flow is shunted from some organs and redirected to the working muscles during exercise. The redirection of blood flow is to adequate supply the working muscles with oxygen and remove the waste products produced from cellular respiration.
Tumours exhibit hypoxia like conditions due to metabolic and blood vessel abnormalities that mean that oxygen delivery is impaired making the tumour rely on the glycolysis energy pathway for the tumour cells energy needs instead of the oxidative phosphorylation pathway. This is termed the ‘Warburg effect’
Exercise is also responsible for activating HIF1ɑ which also enables up regulation of pro-erythrocyte proteins and proteins that promote angiogenesis (increase in vasculature) Several studies have suggested an increase in intratumoral (within tumour) perfusion rate (blood flow) The increase in tumour blood flow sounds counter intuitive and far from being a benefit. However, if blood flow to the tumour is stabilised, would it mean that the tumour will have an increased nutrient supply? Therefore, promoting tumour growth? The counterargument to this is as follows; If the intratumoral vascular network is stabilised, this would increase oxygen supply bringing the tumour to normoxic (normal oxygen levels) conditions, altering tumour metabolism and up regulating AMPK and reducing tumour growth. Furthermore, increased intratumoral blood flow also increases Immune cell infiltration and allows easier access for exogenous chemotherapy drugs conferring a possible survival advantage for the patient.
Credit: Research Gate.Net
Caution must be ascribed when interpreting the effect of exercise on tumour metabolism. There are many other factors and genetic mutations affecting metabolism and tumorigenesis where exercise may or may not have an effect upon. There is still much more research to be done on human models.
Interestingly, there is an increasing body of research that examines the mode of exercise and its effects on cancer risk. Research has suggested that moderate to vigorous exercise lowered the risk of a range of cancers including; colon (23%), breast (12%), renal (12%), prostate (10%), pancreatic, gastroesophageal (18%) and ovarian (11%).
Studies using rodent models of cancer have used various types, duration, distances and intensities of exercise. The researchers postulated a dose dependent relationship between exercise and tumorigenesis. However, they did conclude that more research needs to be done to determine the exercise dose.
We can see why the UK government recommends that the adult population needs at least 30 mins of moderate to vigorous physical activity per day. The benefits of exercise are clear. Moderate to vigorous aerobic exercise and resistance training has been shown to have a positive effect on the prevention of cancer. Cancer patients could also benefit from exercise in combination with other treatments such as surgery, chemo and radiotherapy.
For those of us who are lucky enough not to have suffered cancer, a balanced, healthy diet with plenty of exercise will reduce your overall risk of developing cancer. Increased activation of the immune system. Increased exercise induced vascularisation, altered tumour metabolism and more.
Current fitness and exercise qualifications only make reference to the benefits of exercise and its cancer prevention properties. There is little to no explanation of why this is so. This can be detrimental to the overall task of educating a populace to enable them to prevent the onset of this dreadful disease.
As certain as one can be, current fitness professionals may not possess the knowledge to effectively train a cancer patient. (or a one in remission) Given that cancer will affect at least 50% of the population, the notion that fitness professionals do not have this skill set is alarming.
The way forward is for qualification awarding bodies to revamp their qualifications to include much more content on training different populations other than stereotypes of clients who ‘just wants to get bigger’ or ‘lose weight’. A reality of towns and cities across the UK is that people have all sorts of ailments and idiosyncrasies. The time for catering for a select few is now over as reality catches up with rigid qualification structures, content and teaching practices.
This is where SFE Academy is different, the courses we offer have been ‘reality checked’ meaning that we have put the course through quality checks to make sure that what we teach you is relevant to the people you are likely to encounter.
We work closely with industry partners to make sure that once qualified, you are ready for the fitness industry. .
Gene doping is the use of DNA to alter how a gene works. It involves injecting new DNA into the body directly for the sole purpose of enhancing performance of an athlete. The world anti-doping agency (WADA) is the international organisation tasked with ensuring sport is free from doping. Its core vision is “A world where all athletes can compete in a doping-free sporting environment.”
WADA has undergone its fair share of criticism of late. The uncovering of systemic doping by athletes of the Russian federation in collusion with the authorities and the unsubstantiated counter claims made by them against other nations has sown discord and doubt in the public mind’s eye about the effectiveness of the international governing body that is supposed to prevent these kinds of abuses. Is a higher game afoot? A kind of 3D chess among competing geopolitical interests, although using the syringe as a chess piece? This article aims to examine the new frontier in performance enhancement, its leaps, its bounds and how we all might have to face its consequences.
The Human Genome project (HGP) was an international research project to map all of the genes in all Human beings. The HGP project completed the sequencing of all Human genes. The circa 25,500 genes that form the hereditary blueprint for all Humans is now used across the world in research laboratories to try and understand how the genes are expressed. The HGP has had direct and indirect influences in fields as diverse as forensics, agriculture, molecular medicine, microbial genomics, and archaeology and now it seems sport too.
To understand the role of gene doping in sport and exercise it is necessary to have an overview of the current state of gene technology and from the starting point of the HGP. These are some of the key developments in this field.
There are two main ways that genes are regulated; control of transcription (DNA converted into its complimentary RNA code – think of a coat zip being undone) and translation (messenger RNA (mRNA) is used to make amino acids that make up proteins in your body) and changes in the structure of DNA. Your DNA is a blueprint for the production of proteins which make up you. The blueprint is made up of four different bases; Adenine (A), Cytosine (C), Thymine (T) and Guanine (G). In RNA, Thymine is replaced with Uracil (U). The bases link up with specific bases to form base pairs; A&T, C&G.
Mutations are ways that the DNA can be altered and in some cases the alteration of DNA has effects on the way a protein is made and the gene is expressed. One example of this is a point mutation. Mutations to individual bases can be introduced by either substituting a base with another base or when a base pair is either substituted or deleted. Furthermore, an example of a point mutation is Tay- Sachs disease, Cystic fibrosis and Sickle cell anaemia.
There are a number of ways in which gene doping can potentially enhance performance. The up-regulation of some cellular functions in certain organs and tissues that lead to enhancing the capacity of the tissue or organ to deliver increased performance. There are a number of candidate genes that if tweaked, could lead to performance enhancements.
Red blood cells (erythrocytes) are cells responsible for the transport of oxygen from the lungs to the cell and carbon dioxide from the cell to the lungs. It is easy to see why this would be a target for genetic manipulation for the purposes of performance enhancement. Erythropoietin is a hormone responsible for the production and maturation of erythrocytes.
Credit: Human Genome Research Institute
90% of EPO is produced in the kidneys whilst the remaining 10% produced in the Liver. Furthermore, the production of erythrocytes is regulated by the concentration of oxygen circulating in the body. In normal oxygen concentration conditions (normoxia) of the body, the activation of hypoxia-inducible transcription factor 1 alpha (HIF1α) is curtailed. As a result, the production of red blood cells in the body ameliorated. However, in conditions where oxygen levels are low (hypoxia) HIF1α binds to the Erythropoietin (EPO) gene leading to the gene being up-regulated which leads to increased levels of EPO. Therefore, the production of erythrocytes will increase as will the haemoglobin and haematocrit levels.Furthermore, this leads to an increase oxygen and carbon dioxide carrying capacity of the body. Ergo… increased performance.
IGF1 is produced in the liver and is controlled by growth hormone. The release of IGF1 stimulated by sleep, low blood glucose levels, hypoglycemia, high intensity exercise and low levels of IGF1 itself. This in turn stimulates the pituitary gland to release growth hormone which then releases IGF1.
IGF1 has a role in muscle building (hypertrophy) this leads to increases in muscle power. Therefore, performance. It has been postulated that copies of the IGF1 gene could be inserted into muscle cells to cause hypertrophy. This could be valuable for strength and power events such as weightlifting and sprinting.
Oxygen, carbon dioxide, nutrients and metabolic waste are all delivered or extricated by the vascular system. The body has a series of vessels connected to all organs and tissues for this purpose. Also, VEGF promotes the growth of the existing vasculature in a process termed angiogenesis. Whereas, FGF has a role in angiogenesis and tissues repair. The idea is that when copies of the gene coding for VEGF or FGF are introduced into muscle, this then will have the effect of promoting angiogenesis and increase muscles blood supply as a result.
The role in sports performance is that a greater vascular micro structure results in increased oxygen deliver to the muscles and greater energy production for exercise.
The Vascular System.
Alpha Actinin 3 (ACTN3) is postulated to play a role in fast twitch muscle contractions. This type of muscle fiber (fast twitch) is different from other fibers primarily by the way in which energy is derived for muscles contractions and how efficient the fiber is at producing energy from that ‘energy system’. ACTN3 has been termed the ‘speed gene’. A recent study suggests that ACTN3 plays an important role in muscle metabolism and the fatigability of the muscle. However, the study does not suggest that it plays a role in muscle hypertrophy.
ACTN3 would be an obvious candidate for genetic manipulation to enhance speed performance in athletes. However, if ACTN3 were to be down regulated to cause a deficiency, there could be a performance benefit for more endurance trained athletes.
PPAR’s play a role in cell differentiation and metabolism. There actions differ between to the four subsets but their use for the performance enhancement is interesting. They play a role in fat (lipid) metabolism, glucose homeostasis and insulin sensitivity. All three would be beneficial to an athlete interested in surreptitiously improving performance. Lipid metabolism in the liver and fat cells (adipocytes) is regulated by PPARα as is the breakdown (catabolism) and β oxidation of fatty acids (lipid metabolism). PPARβ, δ and γ on the other hand are responsible for the metabolism of glucose.
The up-regulation of these genes would provide benefits in the increase in uptake of glucose by the cell. Therefore, increasing energy metabolism for exercise. Increased β oxidation would also provide benefits to energy production for exercise but it would also help athletes who need to ensure they are in the right weight category during competition such boxing, MMA and even bodybuilding.
If the PPAR gene expression is exploited, it is also easy to see how this could easily cross into the main stream from elite sport. The proliferation and widespread abuse of anabolic steroids and growth hormone in gyms and health clubs today only reinforces the idea that societal pressure placed upon people to look good can lead people down all sorts of quick fix avenues.
Several studies have assessed the possible candidates for altering the expression of certain genes that govern emotional control, stress and an athletes outlook during competitions. There are two main gene candidates in this regard; serotonin transporters (5HTT) and Brain-derived neurotrophic factor (BDNF). Altering the expression of these genes could produce improvements in all of the above psychological factors to accompany any physical changes the athlete experiences due to gene doping.
Altering the genes to enhance performance, is this cheating? Is this dangerous? Or is it inevitable? Gene doping raises some obvious ethical arguments. Because the pace of change in the field of genetics means that we are fast approaching the point at which we will be in a world where athletes routinely alter their genes to gain the advantage. However. this has ramifications for us all. The use of anabolic steroids in the competitive bodybuilding in the 60’s and 70’s and the subsequent rise of the health and fitness industry in the intervening time has leached into the mainstream.
Should we expect this to cross over too? Will society deal with it when gene doping does come along and what are the implications for society when we are in the era when gym members start to artificially alter the ways their genes are expressed just to look good? One could also argue that we all inherit DNA, chromosomes and genes from successive generations with their own unique mutations. Some beneficial, some not so and some fatal.
Why is Usain Bolt so fast? Is it to do with how ACTN3 is expressed and used in his muscles? What if another 100m runner didn’t have the same mutation as Usain Bolt or other runners. Therefore, giving a genetic disadvantage.
By artificially altering our genes aren’t we just introducing mutations in a controlled way and leveling the playing field?
In conclusion, It has only been since 2003 that we managed to map the Human genome. Although the pace of change in the field of gene editing, therapy, molecular medicine and others are increasing exponentially. However, we are still in its infancy and there is a lot we have yet to learn and the dangers have not yet been fully realised.
Gene Doping: Editing the your way to performance?
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