A study carried out by Duke University Medical Center, and funded by the Howard Hughes Medical Institute has just been published in the peer reviewed journal Nature. The study investigated the affect of adrenalin on DNA and any damage caused. If you read the newspaper though you could be forgiven for thinking that the study was far wider ranging.
The Sun managed the headline “When the going gets tough, the tufts get greying,” whilst the Daily Mail managed to glean that “this DNA damage might cause stress to bring on cancer”. Many other newspapers speculated that stress causes grey hairs. How they managed to come to this conclusion from a report which did not even address this point is open to speculation.
The study was based on laboratory research. Mice were which infused with a substitute for adrenaline for four weeks. After the month they were found to have DNA damage and reduced amounts of a protein called p53. Researchers believe that there is an association between p53 and tumours forming. If lower levels of p53 occur then the protection given by the protein to our DNA is not enough and the likelihood of a tumour forming increases.
The study identified a reaction where the DNA in a cell was damaged because of the adrenalin. The tests themselves were only conducted on mice and cells and cannot be said to replicate a stressful situation in humans. The method of infusing the mice with the adrenalin is contrary to how humans receive adrenalin. In humans the body produces adrenalin in response to a perceived threat but does not continually supply the body when no threat is present. It may replicate a body that is subjected to chronic stress but the researchers do not yet know how that system works in humans. They are aware though that the stress hormone cortisol is involved with humans with chronic stress.
There was no identification of any changes to the level of risk of the mice developing cancer or heart problems after the testing. However further investigation into the affects of chronic stress and any outcomes such as heart disease or tumour are warranted after this piece of research.
The Research Phase
The hormone adrenalin was used on mice to investigate any reactions in the cells caused by exposure to adrenalin. Human cells were also used as part of this laboratory study. The aim of the study was to investigate associations between DNA damage and adrenalin. Adrenalin is sometimes described as the chemical in our body that responds to the fight or flight scenario. This is because of the responses it can cause if we find ourselves in a dangerous situation.
It was discovered that a cell had a series of reactions take place causing p53 levels to drop. p53 is a protein believed to prevent tumours developing by regulating the process of cell division. This is one of the reasons that this protein is so interesting to research into cancer.
Because the study investigated cell biology pathways in mice and human cells it could never be able to identify physical symptoms of an action noted. This means that the theoretical link between stress and grey hair could never be proven or unproven by this study.
The actual steps taken by the researchers started by infusing mice either with artificial adrenaline (isoproterenol) or a salt solution for four weeks. During this period they investigated whether there was DNA damage. The method used to do this involved checking for chemical changes to histones, the proteins which surround the DNA. Changed histones is one of the earliest pointers to DNA damage.
The thymus, which is the specialised organ of the immune system, was then investigated. Amongst the further examinations carried out on cells were tests into the effect of isoproterenol on human bone cancer cells and skin cells and tests to identify what types of adrenaline receptors were behind the changes in p53 levels. This was done by using inhibitors that blocked certain subtypes of adrenaline receptor from working the numerous proteins in the cell. These proteins are linked to the process which causes the cell p53 to be located in a certain place. Checks were done to see how these proteins responded to the isoproterenol. Ultimately a genetically modified mouse which did not produce beta-arrestin 1 was produced. Beta-arrestin 1 is one of the proteins found to be linked with the adrenaline (isoproterenol) response.
It was identified that 4 weeks is long enough to cause DNA damage when the mice were subjected to continual infusion. This then caused the p53 protein levels in the thymus to drop. When replicated in the cells the experiment produced the same results.
Further findings showed a drop in p53 levels because the isoproterenol caused the p53 to be broken down by proteins within the cell and p53 was removed from the centre of the cell. That is where the DNA is situated.
It was discovered that beta arrestin 1, AKT and MDM2 were associated with drop in p53 levels. These three proteins were activated at different stages causing the MDM2 protein to bind with the p53 protein and then break it down. It was further discovered that the mice which did not create the beta arrestin 1 protein, when exposed to isoproterenol showed less DNA damage.
This lead the researchers to associate beta-arrestin 1 with some emerging roles in protein clearance pathways indicating that DNA damage may build up in response to chronic stress.
Analysis of protein reactions at the cellular level were analysed whilst subjecting cells to adrenalin exposure. The findings conclude that DNA damage can be caused by exposure to adrenalin. Until further research takes place with humans then opportunities for greater gains are limited.
It is expected that this study is a first step and further research with mice to explore these proteins will take place. An issue with the testing procedure is the possible mismatch in the amount and method of exposure to the adrenalin that the mice were subjected to. It is still not clear how much adrenalin in comparison to a human in a stressful situation the mice were given.
The study also administered the adrenalin slowly over the period of a month, the human body produces adrenalin in response to an immediate situation. However there is a valid argument that if someone suffers from chronic stress then the adrenalin is being produced continually. This is an area which needs further research to assess the methods of adrenalin delivery. Whether a generally stressful period of time causes the body to deliver different amounts or in a different fashion from a one off situation requires further research.
The research was formed in such a manner that no physical outcomes of stress could be found. All research was at a lower level and could identify issues at the DNA and protein levels but how this would show itself as a symptom could never be identified. As a first stage research project all work and results were satisfactory. It now leaves the door open for further work on many facets of adrenalin and stress. Maybe in the future it will be confirmed that grey hair really is a symptom of stress. That way the newspapers can have another scoop.