DNA and Christmas Tree Lights

Another video from Nessa Carey, explaining the structure of DNA.  As I said in the last post she explains things really well.

The Epigenetics Revolution: DNA is a script not a template

Friday night we went along to another lecture at the Edinburgh Science Festival.  This one was on one of my trinity of sexy subject (mitochondria, the microbiome and epigenetics).

Nessa Carey was the lecturer and she was talking about epigenetics.  It was a really good talk.  What made it very helpful was the way in which she used good illustrations to explain the complexities of epigenetics.  

She talked about how DNA is not a template to make lots of identical clones, but a script:  her example was Romeo and Juliet....the words can be the same but what comes out at the end on stage or screen can be totally different.



Another one she had relating to disease as much as anything was the idea of a bicycle.  The bike can be fine, everything functioning and ready to go.  However, if it is locked to a fence it will not be going anywhere.  Nothing wrong with the bike, but until it is released then it will not function.  Similarly your DNA can be fine with the code for all sorts of health, but if some environmental factors ar limiting it then the potential will never be expressed.

Some of her historical stories were fascinating too, like the Dutch Hunger Winter and its impact on the health of children and grandchildren of those who suffered at that time.

Her other useful example was a set of diagrams using sweets / candy to explain the structure of DNA....there is a pdf on her site which presents her model
and of course the video!

I might buy her book when I get a bit more time to read.

My question for her was how to unlock my bike to reach my full potential.....

Your epigenetics make you fat

I think I have remarked before on this Trinity of sexy themes at the moment in research in health and fitness:

• Microbiome
• Mitochondria
• Epigenetics

This is one for the epigenetics thread:  remember you have genes but the key thing is which of those genes are turned on  and which are turned off.  You are not programmed by you DNA, it is far more complex than that - you have a complex set of switches that react to your environment.

And that applies to your obesity.  You are not programmed to be fat.  Even if you have certain genes that are associated with fatness, they can be overridden.  The environment, epigenetic factors, the signals that you send to your cells,  are so much more important.  So to the study:


Getting Active Blunts Fat Genes

Physical activity appears to dampen the effect of fat-increasing genes, while inactivity allows the genetic disposition to unfold, a longitudinal study found.

Each additional gene variant linked with increasing body mass index (BMI) was associated with a mean gain of 0.13 kg/m2 in BMI, according to Qibin Qi, PhD, from Harvard School of Public Health in Boston, and colleagues.

However, individuals who were most physically active saw a blunted genetic effect, with a mean increase of 0.08 kg/m2, while those watching more than 40 hours of TV per week had an accentuated effect, with a mean increase of 0.34 kg/m2.

Although the genetic effect on BMI was most pronounced at each extreme, it was less so with more benign lifestyles, researchers reported at the American Heart Association's Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism (EPI/NPAM) meeting in San Diego.

For those in the lowest quintile of physical activity, the mean increase in BMI was 0.15 kg/m2 -- a number slightly higher than the reference mean gain associated with each gene variant.

For those who watched up to only one hour of TV per week, the mean gain in BMI was 0.08 kg/m2, the same as in the highest quintile of activity.
 

 You do not have to be fat.  Get up and move about a bit.

Our plastic muscles....coffee and exercise

Back to our sexy themes...this time it is epigenetics:

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

Highlights

• Transient promoter methylation occurs after an acute exercise
• Ex vivo muscle contraction mimics exercise-induced hypomethylation
• Caffeine mediates DNA hypomethylation in myocytes, implicating a role for Ca2+ release
• Summary

DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.

 Exercise is an environmental factor that affects gene-expression, i.e., which genes are made active.  Exercise itself has immediate impacts on your DNA.   The wierd thing about this study though is that caffeine also has similar impacts.  Again it is an environmental factor that affects gene expression.

The New Scientist explains it this way:

Now there is no excuse to avoid the gym: just one hour of exercise instantly changes your genes to boost the breakdown of fat.

Juleen Zierath and Romain Barrès at the Karolinska Institute in Stockholm, Sweden, and colleagues looked for epigenetic changes – the addition of a methyl group to genes – in muscle cells during strenuous exercise. To do so, the team collected biopsies from the thigh muscles of eight men who led relatively sedentary lives, both before and after an hour of exercise.

Several genes involved in fat metabolism that were methylated before the exercise lost their methyl group. Such demethylation allows genes to more easily make proteins, which suggests that more proteins involved in the breakdown of fat are being made after exercise, says Zierath.

The group was surprised to see these effects happen so quickly. They think calcium, produced in muscle cells during exercise, may be involved since subjecting the same biopsies to caffeine – which also increases calcium in muscles – caused the same demethylation.

Unfortunately, you would get caffeine intoxication before gaining the same effects from coffee as an hour-long workout, says Zierath.

Here is how Science Daily explained the story:

The new study shows that the DNA within skeletal muscle taken from people after a burst of exercise bears fewer chemical marks (specifically methyl groups) than it did before exercise. Those changes take place in stretches of DNA that are involved in turning "on" genes important for muscles' adaptation to exercise.

When the researchers made muscles contract in lab dishes, they saw a similar loss of DNA methyl groups. Exposure of isolated muscle to caffeine had the same effect.
Zierath explained that caffeine does mimic the muscle contraction that comes with exercise in other ways, too. She doesn't necessarily recommend anyone drink a cup of joe in place of exercise. It's nevertheless tempting to think that athletes who enjoy a coffee with their workout might just be on to something.

Broadly speaking, the findings offer more evidence that our genomes are much more dynamic than they are often given credit for. Epigenetic modifications that turn genes on and back off again can be incredibly flexible events. They allow the DNA in our cells to adjust as the environment shifts.

It is all getting epigenetic now

Reading through a few abstracts today I was noticing how lots of research is looking at epigenetics - how environmental factors affect the status of genes - which ones are turned on or off to over simplify things. Here is a typical one

Effects of mild-exercise training cessation in human skeletal muscle

Stoppage of endurance exercise training leads to complete loss of maximal oxygen uptake (VO2max) gain but not submaximal exercise blood lactate concentrations. However, the detailed mechanisms are still unknown. Thus, we investigated the effects of exercise-training cessation at lactate threshold (LT) intensity on physiological adaptations and global mRNA expressions in human skeletal muscle. The VO2max, muscle capillaries density and global gene expression were measured after 12 weeks of LT training, and after 12 weeks of detraining. Twelve weeks of detraining reversed the effect of 12 weeks LT training on VO2max and VO2 at LT intensity, although the later value was higher than the pre-training level. Moreover, the training cessation did not affect the number of capillaries around type I fiber, which was increased by training. The training modulated 243 characterized transcripts, in which 77% showed a significant reversible effect by detraining. However, the transcripts most-induced by the training were still elevated after the same period of detraining. The pathway and network analysis revealed that these genes were related to oxidative phosphorylation (OxPhos), calcium signalling and tissue development. Therefore, these physiological and transcriptional changes suggest improved oxygen supply and OxPhos in the skeletal muscle, which may contribute to the incomplete loss of absolute VO2 at LT intensity after training cessation. The present study does not only demonstrate, for the first time, sustained effects of training after detraining at the transcriptional level, but also indicates the possible signalling pathways.

The researchers are no longer just looking at what the exercise or cessation of exercise does directly to the body.   Beyond that they are looking at how exercise changes gene expression.  In this case, exercise seems to have long lasting impacts on the genes that enhance oxidative phosphorylation (OxPhos), calcium signalling and tissue development.  These changes persist even when people stop training.

It is really fascinating.  Exercise changes what your genes set you up for.

Epigenetics again

At the moment everything seems to be about  epigenetics, mitochnodria or the microbiome.

Here is one about epigenetics - turning genes on or off:

Scientists at the University of California, San Francisco (UCSF) have identified nearly 200 genes in the healthy prostate tissue of men with low-grade prostate cancer that may help explain how physical activity improves survival from the disease.

Vigorous exercise linked to gene activity in prostate