Gene Mutation Provides Resilience to Cold

According to a paper published today in the American Journal of Human Genetics, the protein α-aktinin-3, which is found only in fast-twitch fibers, is absent in almost 20% of people due to a mutation in the gene that codes for it. As a result, more of the skeletal muscle of these individuals comprises slow-twitch muscle fibers, which are more durable and energy-efficient and provide better tolerance to low temperatures than fast-twitch muscle fibers.

"This suggests that people lacking α-aktinin-3 are better at keeping warm and, energy-wise, at enduring a tougher climate, but there hasn't been any direct experimental evidence for this before," explains Håkan Westerblad from Karolinska Institutet, senior author of the study. "We can now show that the loss of this protein gives a greater resilience to cold and we've also found a possible mechanism for this."

For the study, 42 healthy men between the ages of 18 and 40 were asked to sit in cold water (14 °C) until their body temperature had dropped to 35.5 °C. During cold water immersion, researchers measured muscle electrical activity with electromyography (EMG) and took muscle biopsies to study the protein content and fiber-type composition.

The results showed that the skeletal muscle of people lacking α-aktinin-3 contains a larger proportion of slow-twitch fibers. On cooling, these individuals were able to maintain their body temperature in a more energy-efficient way. Rather than activating fast-twitch fibers, which results in overt shivering, they increased the activation of slow-twitch fibers that produce heat by increasing baseline contraction.

"The mutation probably gave an evolutionary advantage during the migration to a colder climate, but in today's modern society this energy-saving ability might instead increase the risk of diseases of affluence, which is something we now want to turn our attention to," says Professor Westerblad.

Another interesting question is how the lack of α-aktinin-3 affects the body's response to physical exercise. "People who lack α-aktinin-3 rarely succeed in sports requiring strength and explosiveness, while a tendency towards greater capacity has been observed in these people in endurance sports," he explains.