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How will ‘couch potato’ humans evolve? Idle cavefish offer clues.

The idle Mexican cavefish, which adapted to a more sedentary lifestyle, is seen above the fish of the same species that remained at the surface. (Stowers Institute)
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Humans sheltered in place for weeks early in the coronavirus pandemic, allowing what was already a sedentary lifestyle for many people to descend into endless hours attending Zoom meetings, streaming movies and awaiting food deliveries.

Yet in the realm of couch potatoes, we’re amateurs.

A species of fish washed by floods into dark Mexican caves has been essentially sheltering in place for the last 160,000 years, undergoing genetic changes that reset its metabolism, according to a new study in the Proceedings of the National Academies of Sciences. Over thousands of generations, the Mexican cavefish has adapted to life huddled away in the fish equivalent of a dingy den with little light or food; it has learned to swim slowly, starve for long periods, and get by with less muscle mass and more fat.

But don’t expect their long-term success in the slow lane to impress your doctor into recommending a regimen of more hours in front of the computer and the television, with generous nap times in between. A lifetime of inactivity puts people at higher risk for heart disease, obesity, high blood pressure, high cholesterol, stroke, Type 2 diabetes and some cancers.

How sitting all day can cause health problems — even if you exercise

“What I felt was interesting is that in humans, it has been long understood that a sedentary lifestyle leads to pretty negative health outcomes, but those come within a lifetime,” said Joshua Gross, an associate professor of biology at the University of Cincinnati who was not involved in the new research.

“This study provides an idea of how inactivity can play out not just in a lifetime, but [in] long-term evolutionary changes.”

Because inactivity is so bad for human health, it is considered unethical for scientists to carry out experiments comparing groups of active and inactive people.

Thanks to cavefish, however, they don’t have to. When floods carried some Mexican tetra river fish, Astyanax mexicanus, into about 30 different caves, other fish of the same species remained at the surface, providing a natural study in contrasting evolutionary paths.

Surprising as it may sound, the cavefish is a good model from which to examine the possible long-term developmental changes that may lie in store for humans should we pass down our passivity over hundreds or thousands of generations.

Humans and cavefish are both vertebrates — animals with backbones — and share about 80 percent of the same genes, said Nicolas Rohner, an author of the study and associate professor at the Stowers Institute for Medical Research, a nonprofit biomedical research organization in Kansas City, Mo.

For years, scientists have studied blindness and loss of pigmentation in cavefish to better understand these conditions in humans. They’ve found that one of the four genes in people that can mutate and cause albinism is also crucial to albinism in cavefish. Moreover, obesity in both species can be traced to mutations in a gene they share.

Some of the same circumstances also account for idleness in both species.

“Cavefish move less because they have no predators,” Rohner said, explaining that modern humans enjoy the same luxury. In the pools where cavefish dwell, there are no currents to push against, meaning that when they swim, they face little resistance. As for humans, many have developed a car-dependent lifestyle in which there is far less need for walking, which means we collectively spend less time propelling our legs uphill or pushing our bodies against a stiff wind.

In his lab, Rohner has reared about five generations of both cavefish and surface fish. He and his colleagues tested wild and lab-reared versions of the fish, comparing everything including swimming speed, body composition, organs, tissues and even protein levels.

The scientists found that cavefish swim about 3.7-fold slower than fish that lived outside caves. Since cavefish had no need to employ the kind of burst-swimming needed to elude predators, they evolved into slow continuous swimmers.

The team also discovered the genetic underpinnings of certain traits. In cavefish, groups of genes that contribute to the wasting away or loss of muscle tissue were turned up, meaning they had lower muscle mass than those that had remained outside the caves. However, genes that regulate swimming speed and the ability of muscles to contract were turned down.

“It’s one of the most thorough studies I’ve seen,” said William Jeffery, a distinguished professor of biology at the University of Maryland who has studied cavefish for more than 20 years. “That work done in the laboratory was then taken into the field and confirmed ― I don’t think I’ve seen that in any study like this done so well.”

Jeffery added that the study is the first to show that cavefish experienced a trade-off in the course of their evolution: losing muscle but accumulating fat.

The scientists discovered a curious contrast between the wild and laboratory-reared fish when it came to the size of muscle fibers. Usually smaller muscle fibers are associated with less vigorous swimming and muscle atrophy.

“We were surprised to find that laboratory cavefish had larger muscle fibers than laboratory surface fish,” Luke Olsen, a co-author of the paper who is a graduate student in Rohner’s lab, wrote in an email. However, the scientists found just the opposite when they examined wild fish: The cavefish had smaller muscle fibers than the surface fish.

Olsen said they believe the reason is that cavefish get more food in the laboratory than they would in the wild.

The darkness of caves does not permit photosynthesis, the process plants use to convert sunlight into energy and generate oxygen. The lack of plant life has posed a challenge for cavefish. Some populations share caves with bats and derive nutrition from bat guano that enters the water. Other cavefish feed on cave crickets and consume microscopic crustaceans carried inside by drips though the ceiling. In general, however, they must cope with a scarce food supply compared with surface-dwelling fish.

In the lab, cavefish convert the more generous food supply into sugars and fats, which get stored in the muscle fibers, causing them to grow larger.

“It appears cavefish have rewired the traditional role of muscle fibers” in muscle contraction, Olsen said. The cavefish use their muscle fibers as “a storage site for fuel reserves.” It is the stored excess fat that helps the cavefish get through periods of starvation of a month or longer.