It is common knowledge that it is very dangerous to be inactive and that regular physical activity brings health, improves quality of life and extends life span. How these positive effects are created in the body is not known. Influences on gene activity in the heart, vessels and muscles are probably immensely important.
In this study, the first of its kind, Drs James Timmons, Carl J Sundberg and co-workers show that hundreds of genes are activated by regular cycle training for six weeks in young healthy men. Some of these genes are most likely linked to diabetes and cardiovascular disease. These training study findings can therefore be important for the development of new treatment strategies for such diseases.
Some people respond more easily to training than others. It is not known what explains this. The results from the training study show that those individuals that improved their performance most also activated several genes in the muscles markedly more. This has not been shown before.
Finally, the researchers made a comparison between the effects of endurance training and the situation in patients with Duchenne ™s muscle dystrophy, a muscle wasting disease. Most of the muscle genes previously claimed to be specific for Duchenne were also activated with endurance training. Maybe the musculature in Duchenne patients strive to adapt in part similar to what happens in training. The results from this study will help to clarify which genes are uniquely affected in Duchenne.
info.ki.se
In order to define which genes discriminate between those patients who respond to therapy to those who do not, microarray technology, based in a Banting and Best Department of Medical Research laboratory at University of Toronto, was used to analyze the pattern of genes in all participants. This technology allows scientists to compare levels of expression for tens of thousands of genes on a glass slide “ these "gene chips" are the size of a postage stamp. The technology is able to quickly scan the expression of those genes and differentiate between genes which are "turned on" or "turned off". Comparing "genetic fingerprints" allows researchers to rapidly and effectively identify sensitive genetic changes associated with various stages of disease, and hopefully identify the most suitable candidates for specific therapies.
"We went into this experiment without any hypothesis about what to look for," said Aled Edwards, a Professor in the Banting and Best Department of Medical Research at University of Toronto with cross appointments in the Departments of Medical Biophysics and Medical Genetics and Microbiology. He is also a senior scientist at the Clinical Genomics Centre at the University Health Network and Director and CEO of the Structural Genomics Consortium. "We cast a very wide net, looking at 19,000 genes of each of the patients."
The researchers found that the difference between those patients who did not respond to therapy to those who did was a subset of 18 genes. In the non-responders to treatment, 16 genes were turned on and two were turned off. Many of the 16 genes which were turned on are stimulated by interferon, one of the key antiviral agents that the body produces in response to viral infection and a medication that patients currently receive as part of their therapy. "Paradoxically, in the non-responders, the liver is revved up and the genes are responding like mad, but there is something about the response that just does not work," said Dr. McGilvray.
In the near future, determining the levels of a small subset of genes in patients' liver biopsies, with perhaps a simple blood test, may be helpful in deciding who will respond to treatment of chronic Hepatitis C with the current combination therapy using the synthetic antiviral agent ribavirin and interferon. This treatment can currently get rid of the virus in only roughly 50% of persons infected with genotype 1, the most common genotype in North America and world-wide.
utoronto/