Friday September 21 2007
Gene found in rat cells
Anti-ageing genes have been found which are activated when rats are on extremely low calorie diets, reported newspapers. The Daily Telegraph explained that the discovery could lead to the development of a ‘pill to hold back the ageing process’. Such a pill, the Daily Mail said, would be ‘the so-called elixir of life – [it] could increase lifespan and ward off life-threatening conditions from heart problems to cancer and dementia’.
The newspaper stories are based on a study that found that certain genes in the mitochondria of cells produce a substance that protects the cell from death. Mitochondria are small components of the cell, known as the ‘powerhouse’, they generate the energy that the cell uses to move and function. The study was conducted in the laboratory and on live rats. However, findings in animal studies cannot be directly applied to human beings.
Where did the story come from?
Drs Hongying Yan, Tianle Yang and colleagues from Harvard Medical School and other medical institutions conducted the study. It was funded in part by the National Institutes on Ageing and the National Institutes of Health. Some of the authors have declared an interest in a company that aims to develop and market drug treatments thought to activate the enzymes that control the ageing process. The study was published in the peer-reviewed medical journal Cell.
What kind of scientific study was this?
There were two main parts to the study. The first, and most reported, was the laboratory analysis, which was carried out on cells that had been exposed to an extreme stress (for example, human cancer cells and heart cells that were growing without food, or liver cells from rats that had been starved for 48 hours).
The researchers identified the chemicals that these cells produced in response to the stress situation. They then determined whether this particular chemical (Nampt) could protect cells from the effects of other chemicals which are thought to simulate the ageing process. The researchers explored further exactly how Nampt was able to protect the cells from the effects of these chemicals. Eventually this led them to extract the mitochondria from the cell and identify the genes in it that were responsible for cell protection.
In the second part of the study, the researchers starved rats for 48 hours and then extracted their livers to see whether the cell mitochondria contained the substance that their previous laboratory experiments had suggested protected cells from cell death.
What were the results of the study?
The researchers found that when the cells were exposed to extreme stress (eg starvation), a chain of reactions happened in the cells. A substance (Nampt) was made in the cells that ‘protected’ the cells from death. The researchers were able to pinpoint how this protection was happening and identified certain genes in the mitochondria of the cells that appear to be responsible for it.
After starving live rats for 48 hours, they then found that the mitochondria in the liver cells of these rats had higher levels of protective substances than in rats that had not been starved.
What interpretations did the researchers draw from these results?
The researchers concluded that they observed that levels of protective substances are high in the mitochondria of cells following cell stress. These substances appear able to protect the cell against death (induced by certain toxic chemicals). Their hope is that the findings ‘will facilitate a new understanding of and the development of novel approaches to treating disease such as cancer and neurodegeneration’.
What does the NHS Knowledge Service make of this study?
This is a laboratory study conducted primarily in rats. As always, there is an issue of how relevant the findings from these studies are for human beings. The following points are highlighted:
- Only a small part of this study was conducted on live animals and within this, the researchers did not determine the effects on the actual survival of the live rats. Instead, they extracted cells from the rats’ livers and looked at the concentration of various substances in them.
- It should be noted that there are only four live rats in each of the ‘fed’ and ‘starved’ groups in the live experiment. This is a very small number of rats which is important as smaller studies are known to be less reliable than larger ones. It is unclear whether the researchers analysed the groups in the appropriate way (that is, by rats, rather than by liver samples).
- The news stories extend the findings of this study to protection from ageing in humans. It isn’t clear however, how the study simulates the natural ageing process. In all cases, the cells had been exposed to some form of stress (for the live rats, this was starvation for 48 hours). The protective effect of the stress response was then assessed by exposing the cells to chemicals thought to cause cell death.
- How relevant this study will be for research into the longevity of humans is unknown. That the study heralds ‘a wonder pill that stops ageing in its tracks’ as described by the Daily Mail, seems very optimistic. The researchers have reported useful laboratory work describing the cellular mechanisms, but further research is needed.
Sir Muir Gray adds…
I doubt whether an anti-ageing pill will be discovered in time for me, aged 63, or even my children. However, I already know that many of the changes that we blame ageing for are little to do with the ageing process and are more to do with having lived for a long time; that is, lived for a long time exposed to a western diet or cigarette smoke or inactivity.
The best step to take to combat the effects of ageing is the step you take by putting one foot in front of the other, at least an additional 3000 times each day.