Monday November 29 2010
Mouse health and survival improved after four weeks
“Scientists have managed to reverse the ageing process in a ‘landmark’ study,” reported the Daily Express. The newspaper said that research has shown that targeting the telomerase enzyme proved it is possible to protect body tissue from degenerating.
This research is well-executed and has been described by experts in the field as an important, if not landmark, study. It found that restoring the activity of this enzyme, which protects cells against the damage that occurs as they age, can restore the function of ageing organs in mice.
However, this is research in mice and there is some debate over how applicable these findings are to humans. At present, it should be considered as proof-of-principle that activating telomerase in this way can restore function to cells. More research will probably follow into the effects of artificial induction of telomerase activity. It too soon to describe this as the ‘secret of youth’ and the researchers themselves say that there is more to ageing than the process investigated here.
Where did the story come from?
The study was carried out by researchers from Harvard Medical School in Boston. Funds were provided by the National Cancer Institute and the Belter Foundation. The study was published in the peer-reviewed medical journal Nature.
The research is reported accurately by The Guardian. The Express article may give the impression that a practical application of this research is closer than it actually is, only mentioning that the study is in mice towards the latter end of the article.
What kind of research was this?
This research investigated the ageing process in the laboratory. The researchers were interested in whether restoring the activity of a particular enzyme would affect the age-related decline in the condition of the organs of mice that had been engineered to age prematurely.
Ageing involves many complex cellular processes that drive age-related organ decline and the increased risk of disease. One of these processes involves damage to DNA that can lead to cell death. The DNA damage occurs through the normal course of cell division over a lifetime. At the end of each chromosome is a section of DNA called a telomere. The telomeres protect the DNA from deteriorating. When cells divide, the DNA replicates and each time it replicates, the telomeres at the end of the DNA strands get shorter. When the telomeres get too short, the cell detects this as damage to the DNA and cell death or failure to repair can follow.
Research has shown that an enzyme called telomerase can prevent the telomeres from shortening and may even elongate them. This enzyme is active in many cancer tumours, in which it enables the cancer cells to continue growing. It is a potential target for anti-cancer drugs. Telomerase is not usually active in normal body cells in humans, but the theory is that if it were, the ageing processes involving telomere shortening could be prevented or even reversed.
In this study, the researchers investigated the effects of activating telomerase in genetically modified mice with damaged telomeres and increased DNA damage. They also carried out some of the experiments on the mice cells in culture.
What did the research involve?
Genetically modified mice with no telomerase activity were bred. Researchers tested whether these mice showed premature ageing as would be expected as they lacked the enzyme needed to prevent or slow down telomere shortening. They cultured some of the mutant mice cells (fibroblasts) for four weeks in an environment that reactivated telomerase. Live mice were treated with the telomerase activator too, and the researchers investigated what effect this had on their organs and survival.
The researchers were particularly interested in the effects on brain health (because ageing in humans involves changes to cognition) and on smell (ageing in humans often means “a reduced ability in odour identification and discrimination”). Towards this end, they investigated the effects of inducing telomerase activity in neural stem cells (the cells that produce other brain cells) of these mutant mice and on cells specifically linked with the sense of smell.
What were the basic results?
The genetically modified mice had significantly reduced survival (44 weeks compared to the 87 weeks that normal mice are expected to live) and many of their organs were damaged. When the researchers exposed mouse cells in culture to telomerase, an increase in telomere length was observed. Live mice treated with telomerase also displayed growth in telomere length, and also had improved organ health, particularly in the fast-growing cells such as those in the intestines, the testes and the liver. After four weeks of treatment, the mouse survival improved.
In further experiments, mouse neural stem cells that were treated with a telomerase activator had a restored ability to produce brain cells (i.e. neurogenic capacity). Further detailed analyses of the brain cells showed that telomerase activation restored several of the cell features to normal. Olfactory and neural cells that generally had shorter telomeres and were dysfunctional before treatment had their function partially restored afterwards.
How did the researchers interpret the results?
The researchers say that their mouse model has demonstrated the effects of telomerase reactivation in adult cells and different organs, and that it can restore the length of telomeres and reduce DNA damage in mice. They speculate that this may mean that the organs retain some healthy stem cells that can be reactivated to reproduce normal cells. They conclude that their findings warrant further study, saying that “…this unprecedented reversal of age-related decline in the central nervous system and other organs vital to adult mammalian health justify exploration of telomere rejuvenation strategies for age-associated diseases.”
This is well-executed laboratory research in animals and has been described by experts in the field as an important, if not a landmark, study. However, this is research in mice and there is some debate over whether these findings can be applied to humans. At present, it should be considered as proof-of-principle that activating telomerase, an enzyme known to prevent the shortening of telomeres that has been linked to cell damage and ageing, can restore function to cells.
The findings help to explain further some of the complex cellular activities that occur as cells age.
More research will probably follow into the effects of artificial induction of telomerase activity. It is too soon to describe this as the “secret of youth”, as the Express does. The researchers themselves acknowledge that there is more to ageing than the process investigated here.