Almost one in five people lack key protein in their muscle fibers

About one in five individuals do not have the α-actinin-3 protein in their muscle fiber. Now, a research team from Karolinska Institute in Sweden has demonstrated that more of the skeletal muscles of these people contain slow-twitch muscle fibers that are more energy-efficient and long-lasting, and offer greater resistance to low temperatures when compared to fast-twitch muscle fibers. The findings have been published in the American Journal of Human Genetics.

Håkan Westerblad. Image Credit: Mats Rundgren.

Skeletal muscle contains fast-twitch (white) fibers that tire rapidly as well as slow-moving (red) fibers that are more resistant to fatigue. Almost 20% of people, that is, nearly 1.5 billion individuals, lack the α-actinin-3 protein, which can be found only in fast-twitch fibers. This can be attributed to a mutation in the gene that codes for it.

From an evolutionary standpoint, the presence of the mutant gene increased as human beings moved from Africa to the cooler climates of northern and central Europe.

Better at keeping warm

This suggests that people lacking α-actinin-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. 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.”

Håkan Westerblad, Professor of Cellular Muscle Physiology, Department of Physiology and Pharmacology, Karolinska Institutet

In this analysis, a total of 42 healthy men aged between 18 and 40 were asked to remain in cold water (14 °C) before their body temperature had reduced to 35.5 °C. During immersion in cold water, the team quantified the electrical activity of muscles with electromyography (EMG) and obtained muscle biopsies to analyze the content of the protein and the fiber-type composition.

Produce heat in a different way

The results demonstrated that the skeletal muscle of individuals who lacked the α-actinin-3 protein includes a greater amount of slow-twitch fibers. Upon cooling, these people were able to regulate their body temperature in a more energy-efficient manner. Instead of triggering fast-twitch fibers that lead to excessive shivering, these individuals increased the activation of slow-twitch fibers that generate heat by increasing the baseline contraction (tonus).

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.”

Håkan Westerblad, Professor of Cellular Muscle Physiology, Department of Physiology and Pharmacology, Karolinska Institutet

May affect the response to exercise

Another fascinating question is how the absence of the α-actinin-3 protein impacts the body’s reaction to physical activity.

People who lack α-actinin-3 rarely succeed in sports requiring strength and explosiveness, while a tendency towards greater capacity has been observed in these people in endurance sports.”

Håkan Westerblad, Professor of Cellular Muscle Physiology, Department of Physiology and Pharmacology, Karolinska Institutet

One drawback of the research is that it is more difficult to investigate mechanisms in human experiments at the same level of precision as in cell and animal studies. The physiological mechanism described in this study has not been confirmed by experiments, for instance, at the molecular level.