Tuesday August 23 2011
It's not clear how closely the tests mirror human stress
“When the going gets tough, the tufts get greying,” according to The Sun, which was among many newspapers which today reported that stress causes hair to go grey by damaging people’s DNA. The Daily Mail also reports that this DNA damage might cause stress to bring on cancer.
The news is based on laboratory research, which infused mice with an adrenaline-like chemical for four weeks and found that this led to DNA damage and lower levels of a protein called p53. The protein is thought to protect our DNA from damage and prevent tumours forming. This complex research managed to tease out the series of reactions in a cell that led to the DNA damage in response to adrenaline. The study did not look at whether stress caused grey hair, a link which appears to be based on speculation.
As this research was conducted in mice and cells, it is not clear how its results would relate to people with chronic stress. It is particularly unclear whether the constant infusion of adrenaline into the mice represents the way that the body releases adrenaline in people with chronic stress, a condition that also involves other processes such as release of the stress hormone cortisol.
Additionally, this study did not look at the health consequences of this treatment on the mice, e.g. whether they had a greater chance of developing a tumour or heart problems. However, the results of this study warrant further investigation to assess the role of stress in the likelihood of developing disease in humans.
Where did the story come from?
The study was carried out by researchers from Duke University Medical Center, and it was funded by the Howard Hughes Medical Institute. The study was published in the peer-reviewed scientific journal Nature.
The headlines in the newspapers suggested that this study had looked at the effects that stress has on hair greying. In fact, this study had looked at the effect of adrenaline on DNA damage. It was only speculation that this research had potential implications linking greying to stress.
What kind of research was this?
This was a laboratory study which used human cells and mice to investigate the role that stress chemicals play in DNA damage. They were particularly interested in the hormone adrenaline, which is sometimes known as the “flight or fight” chemical due to the responses it can cause in emergency situations.
The researcher discovered a series of reactions in the cell, which lead to changes in the levels of a protein called p53. This protein is important in regulating how a cell divides, and it is thought to have a role in preventing mutations in DNA and tumours occurring. Because of this role the protein is of interest in current cancer research.
This study was looking at cell biology pathways in mice and human cells. As such, it cannot say what physical symptoms too much stress would typically cause in humans, i.e. grey hair, or indeed what constitutes too much stress.
What did the research involve?
The researchers infused mice either with artificial adrenaline (isoproterenol) or a salt solution for four weeks and looked at whether it caused DNA damage by looking at chemical changes to histones, the proteins which package the DNA. Alteration of the histones is thought to be one of the earliest indicators of DNA damage. They then looked at p53 levels in the thymus (a specialised organ of the immune system) of the mice.
The researchers then conducted a series of investigations in cells, examining:
- the effect of isoproterenol on human bone cancer cells, skin cells and a type of kidney cell line
- the location of p53 in the cells in response to the isoproterenol
- what types of adrenaline receptors were behind the changes in p53 levels by using inhibitors that stopped specific subtypes of adrenaline receptor from working
- the numerous proteins in the cell which are involved in regulating where in the cell p53 is found, its clearance (breakdown) and its activity, to see how these proteins responded to the isoproterenol
Finally, the researchers produced a genetically modified mouse which did not produce beta-arrestin 1, one of the proteins that they had found to be involved in the adrenaline (isoproterenol) response.
What were the basic results?
The researchers found in the animal experiments that four weeks of isoproterenol infusion was enough to cause DNA damage and a lowering of p53 levels in the thymus organs of the mice. This finding was replicated in the cell studies.
They found that isoproterenol caused a reduction of p53 levels by causing p53 to be broken down by proteins in the cell. They also found that the treatment caused the p53 to be transported out of the nucleus of the cell, where the DNA is found.
The researchers found three proteins that were involved in the suppression of p53 levels. Beta arrestin 1, AKT and MDM2. They deduced that when adrenaline attached to a particular type of receptor this led to the activation of beta-arrestin 1 protein. This then allowed AKT to activate the MDM2 protein, causing it to bind to p53 and break it down. They further found that mice that did not produce the beta-arrestin 1 protein (the first step of this reaction pathway) had less DNA damage when exposed to isoproterenol.
How did the researchers interpret the results?
The researchers highlighted that beta-arrestin 1 may have some emerging roles in protein clearance pathways. They said that their research reveals how DNA damage may accumulate in response to chronic stress.
This laboratory research teased out a complex series of protein reactions in cellular tests. These reactions were then analysed in an experimental mouse model to underpin the finding that adrenaline exposure leads to DNA damage.
Like all animal research, the implications for humans are currently limited and remain to be determined. This research will undoubtedly lead to further study of these proteins, although it is not clear whether the amount of adrenaline the mice were exposed to is similar to the adrenaline levels that could be found in humans during chronic stress.
For example, the primary role of adrenaline is to allow the body to immediately deal with sudden, emergency situations such as physical threats or impending danger, but it is not fully known how the adrenaline system functions in chronic stress. As such, further research would be needed to determine whether the mechanism is of relevance when considering the effects of typical day-to-day stresses or long-term stretches of feeling stressed.
The newspapers have reported that this research could explain why people’s hair greyed or were at higher risk of developing cancer if suffering from chronic stress. This study did not assess the physical symptoms of the adrenaline treatment in the mice (e.g. whether they went on to develop tumours at a higher frequency than non-treated mice).
This early stage research was well-conducted. Following these findings, further research is warranted to assess whether stress reduction techniques can lower rates of disease.