Nearly one in five people do not have the protein α-actinin-3 in their muscle fiber. Researchers at the Karolinska Institutet in Sweden now show that more of the skeletal muscle of these individuals contains slow-moving 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 (white) fibers that get tired quickly and slow (red) fibers that are resistant to fatigue. The protein α-actinin-3, which occurs only in fast-moving fibers, is absent in nearly 20 percent of the people – nearly 1.5 billion individuals – due to a mutation in the gene that codes for it. Evolutionarily, the presence of the mutated gene increased as people migrated from Africa to the colder climates of Central and Northern Europe.
“This suggests that people who do not have α-actinin-3 are better at keeping warm and, in terms of energy, enduring a tougher climate, but there has been no direct experimental evidence for this,” says Håkan Westerblad, professor in cellular muscle physiology at the Department of Physiology and Pharmacology, Karolinska Institutet. “We can now show that the loss of this protein cold is more resilient, 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 water (14 ° C) until their body temperature dropped to 35.5 ° C. During immersion in cold water, researchers measured electrical activity by electromyography (EMG) and took muscle biopsies to study the protein content and fibrous composition.
The results showed that the skeletal muscle of people who do not have α-actinin-3 contains a larger percentage of fibers that move slowly. With cooling, these individuals were able to maintain their body temperature in a more energy efficient way. Instead of activating fast fibers, which results in overt shivering, it increases the activation of fibers that pull slowly, producing heat, by increasing baseline contraction (tone).
“The mutation probably gave an evolutionary advantage during the migration to a colder climate, but in today’s modern society, this energy-saving ability can rather increase the risk of diseases of prosperity, and that is something we want to establish now,” says Professor Westerblad .
Another interesting question is how the lack of α-actinin-3 affects the body’s response to physical exercise.
“People who do not have α-actinin-3 rarely succeed in sports that require strength and explosiveness, while a tendency towards greater capacity is seen in these people in endurance,” he explains.
One limitation of the study is that it is more difficult to study 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 at, for example, the molecular level.
Reference: “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, 17 February 2021, American Journal of Human Genetics.
DOI: 10.1016 / j.ajhg.2021.01.013.
The study was a collaboration with research groups at Lithuanian Sports University in Kaunas, Lithuania, and the University of Melbourne in Australia. It has been supported by grants from the Swedish Research Council, the Swedish National Center for Sport Research, the Lithuanian Research Council, the Swedish Medical Research Association, the Jeansson Foundations, the Swedish Heart and Lung Foundation and the Australian National Health and Medical Foundation Research. Council. Co-author Volker Lauschke is the founding CEO and shareholder of HepaPredict AB and was a consultant for EnginZyme AB.