Karolinska Institutet. Sweden: A
new study from Karolinska Institutet in Sweden shows that long-term
endurance training in a stable way alters the epigenetic pattern in the
human skeletal muscle. The research team behind the study, which is
being published in the journal
Epigenetics
, also found strong links between these altered epigenetic patterns
and the activity in genes controlling improved metabolism and
inflammation. The results may have future implications for prevention
and treatment of heart disease, diabetes and obesity.
“It is well-established that being
inactive is perilous, and that regular physical activity improves
health, quality of life and life expectancy”, says Professor Carl Johan
Sundberg, Principal Investigator at the Department of Physiology and
Pharmacology. “However, exactly how the positive effects of training are
induced in the body has been unclear. This study indicates that
epigenetics is an important part in skeletal muscle adaptation to
endurance training.”
Epigenetics can simply be described as temporary biochemical
changes in the genome, caused by various forms of environmental impact.
One type of epigenetic change is methylation, where a methyl group is
added to or removed from a base in the DNA molecule without affecting
the original DNA sequence. If genes are considered the hardware of
cells, then epigenetics can be seen as their software.
The current study included 23 young and healthy men and women
who performed supervised one-legged cycling, where the untrained leg
served as a control. The volunteers participated in 45 minutes training
sessions four times per week during a three month period. Performance
was measured in both legs before and after training. In the skeletal
muscle biopsies, markers for skeletal muscle metabolism, methylation
status of 480 000 sites in the genome, and activity of over 20 000 genes
were measured.
Results show that there were strong associations between
epigenetic methylation and the change in activity of 4000 genes in
total. Genes associated to genomic regions in which methylation levels
increased, were involved in skeletal muscle adaptation and carbohydrate
metabolism, while a decreasing degree of methylation occurred in regions
associated to inflammation.
An interesting and potentially very important novel finding was
that a majority of the epigenetic changes occurred in regulatory
regions of our genome, so called enhancers. These sequences in our DNA
are often situated far away from the actual genes they regulate, in
comparison to so called promoter regions, which traditionally have been
considered to control most of the gene activity.
“We found that endurance training in a coordinated fashion
affects thousands of DNA methylation sites and genes associated to
improvement in muscle function and health”, says Carl Johan Sundberg.
“This could be of great importance for the understanding and treatment
of many common diseases such as diabetes and cardiovascular disease, but
also for how to maintain a good muscle function throughout life.
Interestingly, we also saw that there were epigenetic differences
between male and female skeletal muscle, which may be of importance to
develop gender specific therapies in the future.”
This work has been funded by grants from the Swedish National
Centre for Research in Sports, Torsten Söderberg Foundation, the
STATegra network within the EU’s FP7, Stockholm County Council, and the
Swedish Research Council.