Flies in space: La Jolla researchers seek to unlock keys to cardiac changes using insects in microgravity
A team of researchers at La Jolla’s Sanford Burnham Prebys Medical Discovery Institute co-authored a study published Nov. 25 that details changes observed in the hearts of fruit flies while in space over two missions — changes that may have implications for the treatment of human hearts both in and out of the atmosphere.
Karen Ocorr, assistant professor and principal investigator in the Sanford Burnham Prebys Development, Aging and Regeneration Program; the program’s director, Rolf Bodmer; and a team of scientists first sent fruit flies into space in 2014 to live on the International Space Station for a month before returning to Earth.
For the record:
2:33 p.m. Dec. 4, 2020This article was updated to correct the spelling of Rolf Bodmer’s last name.
“It was a little bit of serendipity to get into this particular set of experiments,” Ocorr said. The project was a collaboration among a Stanford University cardiologist, NASA researchers and others to write the proposal to send the flies into space in order to observe any cardiac remodeling, or changes in heart shape or function.
Ocorr said fruit flies are an “ideal organism” for the experiments, chosen for their life span, which is less than two months. In that time, “we can figure out what happens to its heart over its entire lifetime,” she said. “One week in a fly’s life is about the same as a decade in a human life, so if we look at 6-week-old flies, they’re old.”
Fly hearts also have a similar structure to those of humans, a tube shape that closely resembles human prenatal hearts before their chambers develop.
“The very simple fly heart is one of the best ways to really focus on the specific cause of the cardiac remodeling,” Ocorr said.
Nanoracks, which makes hardware for the International Space Station, funded the 2014 project and created a box to contain several fruit flies and their required food for their stay in space.
Once back in the Sanford Burnham Prebys lab, the flies (and their hundreds of offspring) underwent a “massive” 24-hour study of the effects of the time in space on their hearts — before the hearts were affected by Earth’s gravity, Ocorr said.
She and her colleagues conducted experiments, collecting tissue samples after analyzing heart function, she said. “We pulled the hearts out and later did biochemical assays on them to see what genes were expressed.”
The researchers found that the flies’ hearts underwent profound structural and biochemical changes. The flies returned with small hearts with reduced or impaired pumping abilities.
Three years later, the SBP team sent another box of flies into space, this time funded by NASA. The second mission is “the punchline of the paper we just published,” Ocorr said, as it allowed the researchers “to test some of the information that we received from” the original study.
She said the second journey verified “some of the things that we had seen in the gene changes,” observed in “protein expression” and proteasomes, a “recycler for cells.”
“When proteins aren’t working right anymore,” Ocorr said, “the proteasome takes these proteins and chops them up into their core components, which are [then] reused in nice, shiny, clean proteins.”
“Those got messed up in the flies on the ISS,” she added. “The proteasomes were massively increased in terms of their numbers, but they clumped. They probably increased because there was a lot of damage going on while on the ISS.”
The changes seem to have been caused by the microgravity experienced on the ISS, Ocorr said.
“We can probably rule out a large effect of radiation,” she said. There is some radiation on the ISS, “but it’s still within the magnetosphere of the Earth. To a large extent, you are protected” from radiation while aboard the space station, she said.
“The only different thing then is the change in gravity,” Ocorr said, noting that some of the flies’ genetically identical siblings who remained on Earth under identical conditions lent further support to the findings.
The researchers’ findings have implications for human astronauts as well as those who aren’t planning a space voyage, she said.
“As we try to go and establish colonies on the moon and other planets, we really need to know how changed gravity affects all of our body systems,” she said. “This is just the first tiny little foray into trying to figure these things out.”
The impact on space travelers would be observed on “extended flights,” maybe as part of a colony on the moon or Mars.
Cardiac remodeling “probably isn’t something that’s going to happen if you’re up in space as a tourist for a week or even a month,” Ocorr said. “It’s probably not even going to affect your heart function so significantly for even half a year.”
But damage to heart function during an extended space stay is “something you want to start worrying about,” she said. “The idea is to figure out what countermeasures we can come up with to prevent some of these cardiac remodeling changes.”
For those staying on Earth, “one of the theories of the effects of microgravity that’s gotten bounced around a lot is that it accelerates aging,” Ocorr said. “So if that’s the case, this may shed some light on that process.”
In addition, she said, “there’s all kinds of literature showing that people who are spending a lot of time in forced bed rest and suffering cardiac problems as a result …. these results may suggest ways to deal with that kind of cardiac dysfunction.”
Ocorr said she and the other researchers “still have a whole lot of data that we are mining from” the flights and that the study so far has “been a fantastic experience; it’s really thrilling to see your experiment take off on a rocket ship and to see it come back. I never thought I would be able to use the words ‘ground control’ in a professional talk.” ◆
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