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Don't Suffer in The Cold? Turns Out There's a Genetic Mutation For That

19 FEBRUARY 2021

Most of us living on planet Earth have to make it through some amount of cold weather for at least part of the year, and new research has identified a specific genetic mutation that makes a fifth of us more resilient to cold conditions.

 

The genetic mutation in question stops the production of the protein α-actinin-3, which is important for skeletal muscle fibre: The protein is only found in fast-twitch (or white) fibres and not in slow-twitch (or red) fibres.

Based on the new study's results, people without α-actinin-3 have a higher proportion of slow-twitch fibres, and one of the consequences is that the body tends to conserve energy by building up muscle tone through contractions rather than shivering.

"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," says physiologist Håkan Westerblad, from the Karolinska Institutet in Sweden.

"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."

The researchers recruited 42 men to sit in 14-degree Celsius (57.2-degree Fahrenheit) water while their temperatures and muscles were measured. The chilly immersion lasted 20 minutes at a time with 10-minute breaks, for up to two hours in total.

 

The proportion of participants who could keep their body temperature above 35.5 degrees Celsius (95.9 degrees Fahrenheit) was higher in those with the α-actinin-3 mutation versus those without – 69 percent of volunteers versus 30 percent.

In other words, the genetic mutation appeared to help these participants to conserve energy more efficiently and build up a greater resilience to the cold.

The team also conducted follow-up experiments in mice with the same mutation in order to check whether having this mutation could have something to do with increasing brown fat stores – a well-known heat-generating tissue in mammals – but that didn't turn out to be the case. 

People lacking α-actinin-3 might be better braced for a cold water swim or a bout of wintry weather, but it could also leave them more vulnerable to obesity and type-2 diabetes if they're inactive, the researchers say. It might also increase the risk of falling as they get older, as fast-twitch fibres handle speedy muscle movements.

"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 [these] diseases, which is something we now want to turn our attention to," says Westerblad.

As previous research has shown, α-actinin-3 deficiency has increased across the population as humans have moved from warmer to colder climes, although questions remain about whether this mutation is present at birth and affects infant mortality.

It's also interesting to note that athletes who excel at sports involving explosiveness and strength (such as sprinting) are more likely to not have this lack of α-actinin-3, while for endurance sports the stats are reversed.

As for future research, the team is keen to look at how this might all work at the molecular level, as well as how it could affect muscle disease. For now, it's an important new discovery about this genetic mutation and the allele or gene form associated with it.

"These findings provide a mechanism for the increase in [these gene variants'] frequency as modern humans migrated from Africa to the colder climates of central and northern Europe over 50,000 years ago," conclude the researchers in their published paper.

The research has been published in the American Journal of Human Genetics.