20% of people have a genetic mutation that offers greater resistance to cold

Almost one in five people lack α-aktinin-3 protein in their muscle fiber. Researchers at Karolinska Institutet in Sweden are now showing that a greater portion of the skeletal muscle of these individuals includes slow-twitch muscle fibers, which are more durable and energy efficient and offer better tolerance to low temperatures than fast-twitch muscle fibers. . The results are published in the scientific journal The American Journal of Human Genetics.

Skeletal muscle consists of fast-twitch (white) fibers that tire quickly and slow-twitch (red) fibers that are more resistant to fatigue. The α-aktinin-3 protein, which is only found in fast-twitch fibers, is missing in almost 20% of people – nearly 1.5 billion people – due to a mutation in the gene that the code. In terms of evolution, the presence of the mutated gene increased as humans migrated from Africa to the cooler climates of central and northern Europe.

“This suggests that people lacking in α-aktinin-3 are better able to stay warm and, in terms of energy, to endure a more difficult climate, but there was no direct experimental evidence for this before. Says Håkan Westerblad, Professor of Cellular Muscle Physiology in the Department of Physiology and Pharmacology, Karolinska Institutet. “We can now show that the loss of this protein gives greater resistance to cold and we have 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 (14 ° C) water until their body temperature dropped to 35.5 ° C. While immersed in cold water, the researchers measured muscle electrical activity by electromyography (EMG) and performed muscle biopsies to study protein content and fiber composition.

The results showed that the skeletal muscle of people lacking α-aktinin-3 contains a higher proportion of slow-twitch fibers. By cooling down, these people were able to maintain their body temperature in a more energy efficient way. Rather than activating the fast twitch fibers resulting in overt chills, they increased the activation of the slow twitch fibers which produce heat by increasing the core contraction (tone).

“The mutation probably gave an evolutionary advantage when migrating to a colder climate, but in today’s modern society, this energy-saving ability could instead increase the risk of abundance diseases,” what we now want to focus on, ”says Professor Westerblad.

Another interesting question is how the lack of α-aktinin-3 affects the body’s response to exercise.

“People who lack α-aktinin-3 rarely succeed in sports requiring strength and explosiveness, whereas a tendency towards greater capacity has been observed in those people in endurance sports,” he explains. he.

One of the limitations of the study is that it is more difficult to study the mechanisms in human studies at the same level of detail as in animal and cell experiments. The physiological mechanism presented has not been verified with experiments, for example at the molecular level.

Reference: “The loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation” by Victoria L. Wyckelsma, Tomas Venckunas, Peter J. Houweling, Maja Schlittler, Volker M Lauschke, Chrystal F. Tiong, Harrison D. Wood, Niklas Ivarsson, Henrikas Paulauskas, Nerijus Eimantas, Daniel C. Andersson, Kathryn N. North, Marius Brazaitis, Håkan Westerblad, February 17, 2021, American Journal of Human Genetics.
DOI: 10.1016 / j.ajhg.2021.01.013.

The study was a collaboration with research groups from the Lithuanian Sports University in Kaunas, Lithuania, and the University of Melbourne in Australia. It was supported by grants from the Swedish Research Council, Swedish National Center for Research in Sport, Research Council of Lithuania, Swedish Society for Medical Research, Jeansson Foundations, Swedish Foundation Heart and Lungs and National Health and Medical Research of Australia. Advice. Co-author Volker Lauschke is the founding CEO and shareholder of HepaPredict AB and has been a consultant for EnginZyme AB.