Will All Those Hours of Training Make You Faster? The Response is in the Genes

We don’t live in Gattaca yet, but the future is coming: in the last several years, scientists have begun to unlock the identity of genes that control humans’ response to endurance training.

“We all have the same genes, but within the genes there is variability so that certain elements of the genes may be different for you or me,” Dr. Carl Johan Sundberg of the Karolinska Institute in Stockholm told FasterSkier in a phone interview earlier this winter.

In other words, the human genome always follows roughly the same map. But at points on that map, individuals could have different specific sequences in their DNA. Some genes are “fixed” in the population, so that everybody has the same copy and there is no variation. Others, however, are “polymorphic”: there are anywhere between two and many copies of the gene circulating in the population, and different copies function slightly differently.

Not everything is controlled by genes; environment plays a big role too, and the two often interact. But what if a skier’s ability to get faster by doing a lot of volume training was controlled by genetics, and polymorphism was the culprit for why your buddy got faster than you did, even though you did the same training? What if genes determined, too, if more intensity training was a better bet than hours of long slow distance?

Anyone who has watched or participated in sports knows that isn’t a crazy idea. And back in the late 1990’s, a study of several hundred adults suggested that the improvement in aerobic capacity, as measured by VO2Max, was roughly 50 percent heritable – that is, dependent on gene copies passed down by their parents, not anything unique to an individual.

Immediately, the researchers asked their follow-up question: which genes accounted for this heritable portion of the response to training? By 2000, an international team led by Drs. Claude Bouchard of Louisiana State University and D.C. Rao of the Washington University of Saint Louis had found several regions of on specific chromosomes that they hypothesized would contain the genes.

By working hard, honing in on these regions in finer detail, and taking advantage of advances in genetic techniques, in 2009 Sundberg and a group of colleagues published another study, indentifying roughly 30 genes that could explain 23 percent of an individual’s gains in performance due to training, or about half of the heritable portion.

“It may be a minor part of it – one out of 1500 [polymorphisms] will make a difference in terms of protein function,” Sundberg said. “We tried to find genes that could explain differences between people. And with endurance training, we did find something that would explain the difference in response.”

How? A Genetics Research Primer

To get to their final result took several steps, and multiple sets of test subjects. Importantly, all of the subjects were untrained, sedentary adults – we’ll get back to what the results mean for athletes a little later.

First, the team took a group of 24 men and put them through a training program, taking a snapshot of RNA expression in muscle tissue before and after the intervention. They found that the training provoked changes in the expression patterns of about 800 genes, which they called the “Training-Response Transcriptome.”

(A transcriptome is simply all of the different RNA produced by a group of cells, and their concentrations. What is RNA? It is produced by copying off of DNA, and has many functions in a cell, from controlling gene expression to synthesizing proteins.)

Some of the genes were expressed more, or “upregulated,” while most were expressed less, or “downregulated.” They likely had a wide variety of functions and controlled many different things in muscle tissue; among those, the team hoped, would be something that determined whether aerobic adaptation took place.

The team then narrowed this down to the 29 best genes that might serve as predictors of training response, and tested them in a second group of 17 study subjects who were also put on a training plan. The prediction was proved true when the expression of these genes correlated to the size of VO2Max improvements in the test subjects.

Finally, the group returned to their large dataset, which is part of what is called the HERITAGE family study. Each of 473 subjects had a personalized 20-week training plan designed based on their existing aerobic capacities. Testing against the VO2Max gains in these 473 men and women, the team found that genetic variation – polymorphism – in a few specific predictor genes was significant in explaining the adaptations.

Even more impressively, the “signature” of these genes could be tested using just 11 single-nucleotide locations in the genetic code extracted from skeletal muscle tissue.

“These variants were common enough in this population to explain the variation,” Sundberg told FasterSkier. “It would explain half of the variability in responsiveness – we found genes that would explain 23 percent of it, which is about half of the genetic component. In the next years, I am sure that there will be studies explaining the other forty percent.”

Can We Predict Olympic Medals?

Sundberg and his colleagues are more interested in public health than in sports – and rightly so. They open their papers by noting that low aerobic capacity is related to inability or lack of exercise, and leads to poor cardiac health and even death. With these studies, they suggest, doctors may be able to tell whether exercise will help their patients gain – back or for the first time – aerobic capacity.

“It is reasonable to state that molecular classifiers (predictors) will be essential for implementing personalized medicine, yet there are limited examples of validated predictors that are able to tailor interventions relevant to the most pressing factors impacting on public health,” Dr. James Timmons, Sundberg, and others wrote in the Journal of Applied Physiology in 2009.

For both cardiovascular health in particular and the emerging field of personalized healthcare delivery in general, the team’s ability to predict and then confirm which genes might determine an individual’s response to treatment was a big step forward.

But what about another application? It’s easy to understand why, if the remaining genes controlling the other half of genetically heritable adaptation are identified, athletes and coaches would want in on this knowledge. They could help tell whether it’s worth pursuing a career into adulthood, how much energy and resources it’s worthwhile for a program to spend on an athlete, or even help identify future stars at a young age.

Let’s not get ahead of ourselves, though. First of all, the training response is not entirely heritable – and the non-genetic component is also incredibly important in determining success.

And even in terms of the genetic component, Sundberg said, the implications for elite athletes are not at all clear. The team was using sedentary subjects, where the range of responses to training was huge. Some saw marked improvement; others didn’t respond at all. What separates one elite athlete from another will be much, much smaller responses, which will be more difficult to detect using these methods.

“When you move to athletes it becomes more difficult,” Sundberg said. “Top level performance is determined by many more genes. It’s extremely difficult to predict who will become a top athlete: we can predict who can respond in a sedentary person, but not who will become a gold medalist.”

For the Curious:

Bouchard, C., Rankinen, T., Chagnon, Y.C., Rice, T., Pérusse, L., Gagnon, J., Borecki, I., An, P., Leon, A.S., Skinner, J.S., et al. (2000). Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study. J Appl Physiol 88, 551–559. Abstract here.

Timmons, J.A., Knudsen, S., Rankinen, T., Koch, L.G., Sarzynski, M., Jensen, T., Keller, P., Scheele, C., Vollaard, N.B.J., Nielsen, S., et al. (2010). Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108, 1487–1496. Abstract here.

Dr. Sundberg’s lab webpage

Dr. Bouchard’s lab webpage

The HERITAGE family study – assessing response to drugs, diet, and exercise