ScienceHealthyLongLife by Crabsallover: Reactive oxygen species (ROS) damage internal cell structure

Wednesday, 2 November 2011

Reactive oxygen species (ROS) damage internal cell structure

reposted from: http://www.nhs.uk/news/2011/11November/Pages/common-drug-may-slow-progeria.aspx

crabsallover highlights, key points, comments / links.

NHS.uk say:-

New pill to halt ageing, papers claim

NHS Choices Wed Nov 2, 2011 15:52

Scientists may have “found a cure for ageing”, the Daily Mirror reported. According to the newspaper, the answer could lie in a “forever young” drug that will allow us to grow old gracefully.

However, this seeminly marvelous news is based on a small study which looked at an extremely rare form of a genetic condition called progeria. This causes children’s bodies to rapidly age and leads to a number of physical health problems, limiting their lifespan to an average of around 13 years.

The researchers examined the cells of people with the condition and found that, compared to cells from healthy individuals, they produced five times the level of ‘reactive oxygen species’ (ROS), chemicals that are damaging to the internal cell structure. These higher ROS levels were associated with more breaks in the cells’ DNA and abnormal cell growth. However, when the cells were treated with a drug called N-acetylcysteine, which is already used to prevent liver damage in people who have overdosed on paracetamol, the researchers were able to largely prevent this DNA damage and improve cell growth and division.

The findings of this study are at a very early stage and suggest some potential ways to help people with rare but devastating forms of progeria. However, it is too great a leap too suggest that the research provides a “cure for ageing”, as some fanciful reports have done.

Where did the story come from?

The study was carried out by researchers from Durham University and the University of Bologna in Italy. It was funded by the European Commission and published in the peer-reviewed scientific journal Human Molecular Genetics.

Most news coverage on the research suggested that it could offer a way to slow or even stop routine human ageing. However, the media’s outlandish claims that scientists are on the verge of a “forever young drug” or a “cure for ageing” are not supported by this research.

Several newspapers focussed on the fact that the study used an existing drug called N-acetylcysteine, and implied that it could soon be used to block the effects of ageing. The drug is currently an ingredient in some eye drops and also has a role in treating paracetamol overdoses and poisoning, for which it is given intravenously for short periods. While it has been proven safe and effective for these uses, there are no guarantees that it would be safe or effective if taken orally in the long term.

Only the BBC’s coverage primarily focussed on progeria, the rare rapid-ageing condition that the research examined.

What kind of research was this?

This study was a laboratory-based investigation into the cause of and possible solutions to the genetic damage that occurs in a group of inherited degenerative disorders called laminopathies. These conditions are caused by mutations in a gene called LMNA, which normally produces a protein called lamin A. The lamin A protein plays an important role in keeping the structures within cells strong and stable.

The study focused on the most severe group of laminopathies, including the rare Hutchinson Gilford progeria syndrome (HGPS), which causes children’s bodies to age too quickly. This causes a range of effects, including restricting growth and loss of body fat and hair. Children with HGPS develop heart disease early in life, and have an average life expectancy of just 13 years.

Laboratory studies are the best way to determine exactly what happens in the individual cells of people with these types of genetic conditions. The results can help researchers explain the symptoms that people develop.

...

Previous studies have shown that skin cells from these patients have high levels of chemicals called reactive oxygen species (ROS). ROS can cause double strand breaks in DNA, and are thought to be involved in the accumulation of this type of DNA damage in normal ageing cells. Therefore, the researchers wanted to test whether ROS might be responsible for the DNA damage seen in cells from patients with laminopathies.

The researchers first compared the level of ROS produced by the cells, and then compared the level of damage caused by ROS in the cells. Specifically, they looked at how ROS caused DNA damage and disruption in the shape of the cells’ internal structures.

Finally, they investigated whether a drug called N-acetylcysteine could reduce the damaging effect of the ROS in the healthy and diseased cells. N-acetylcysteine is a chemical that “mops up” the damaging ROS and is already used to prevent liver damage in patients who have overdosed on paracetamol.

What were the basic results?

The researchers found that:

The cells from people with HGPS had ROS levels that were five times higher than those from healthy individuals.
The high ROS levels were linked to DNA damage (due to double strand breaks in the DNA).
The accumulation of DNA damage in these fibroblasts appeared to cause poor cell growth.
ROS-induced DNA damage could be repaired efficiently in cells from healthy individuals, but could not be repaired in the cells from people with HGPS.
Adding N-acetylcysteine to the cells of HGPS patients led to a significant increase their ability to grow and multiply. The cells also did not develop un-repairable ROS-induced DNA damage.

How did the researchers interpret the results?

The researchers say their findings suggest that the accumulation of ROS-induced DNA damage can “contribute significantly” to the problems seen in the cells of people with HGPS. They also state that N-acetylcysteine in combination with other treatments “might prove beneficial to HGPS patients”.

Conclusion

This laboratory-based study of isolated human cells provides interesting new evidence on how reactive oxygen species (ROS) potentially causes DNA damage in the accelerated ageing condition Hutchinson Gilford progeria syndrome (HGPS). It also highlights that N-acetylcysteine might be of use in treating patients with HGPS.

While this study provides interesting new findings, the following limitations should be considered:

This study experimented on isolated human cells in a laboratory, and it is not known what the effect of N-acetylcysteine would be if it was given to children with the illness.
This is early-stage research, the results of which will need to be confirmed in future studies. The effectiveness and safety of N-acetylcysteine is likely to need to be tested in animal models of the condition before it could be tested in people. However, the fact that N–acetylcysteine is already used as a treatment for paracetamol overdose may mean that human trials could be carried out sooner than for a completely new drug. That said, it would still need to be tested, particular its effects when taken in the long term.
A full randomised clinical trial of N-acetylcysteine may be difficult to conduct as the condition is so rare. The Progeria Research Foundation says that just 78 children are known to have the condition.
The newspapers suggest that the findings are applicable to normal ageing, and that N-acetylcysteine could be a “cure for ageing”. This study focussed on the effect of N-acetylcysteine on the cells of patients with HGPS, a rare, severe genetic condition. It is not possible to say from this study how the findings would apply to the normal ageing process.
HGPS is a genetic condition, and although N-acetylcysteine might be able to reduce or block some of the damage seen in the cells of people with HGPS, it will not remove the genetic mutation itself or allow the body to produce the important lamin A protein.
Regular cellular and physical ageing involves a complex mix of mechanisms. Even if N-acetylcysteine can block some of them, this does not mean that it could stop or greatly slow the overall ageing process.

These findings are at a very early stage and will aid further research into HGPS. However, it may take many years to confirm these findings through other studies and to assess the effects of N-acetylcysteine in HGPS patients. The implications of these findings for the ageing process of people without HGPS is unclear, and it is certainly too early to say that an “ageing pill” is just around the corner.