Spaceflight is no picnic for the body. Muscles atrophy, bones thin, arteries stiffen, inflammation spikes, vision deteriorates—and that’s just for starters. But a new study shows that these disparate effects might have a common cause: out-of-whack activity in mitochondria, the energy-producing compartments in living cells (Cell 2020, DOI: 10.1016/j.cell.2020.11.002). The study is one of a collection of papers on the biological effects of spaceflight published last week in Cell.
The researchers analyzed physiological data collected in space from mice, mammalian cell lines, and 59 astronauts. All of these data had been deposited in NASA’s open-source GeneLab database. These data include levels of genes, proteins, metabolites, and other physiological markers. “The question was, Is there a common switch that is systematically driving a lot of [the body’s] responses and connecting them together?” says Afshin Beheshti, a NASA bioinformatician who works on GeneLab and who led the study. “The thing that kept popping up over and over again is mitochondrial activity.”
The researchers found that across different types of human cells, spaceflight induces changes in levels of mitochondrion-related metabolites and in expression of genes regulating key mitochondrial functions—including synthesizing the energy-carrying molecule adenosine triphosphate and oxidizing nutrients. Changes seen in multiple types of mouse tissues and in living mice sent to space paralleled those present in astronauts. This held for both the Twins Study—which compared astronauts and identical twins Mark and Scott Kelly after Scott spent close to a year in space while Mark remained on Earth—and for blood and urine samples from other astronauts.
Scientists studying specific physiological responses to space had flagged mitochondrial effects before, says Beheshti, but by taking a bird’s-eye view, the researchers could form a more complete picture of what happens in the body. For example, mitochondrial activity in muscle tissue is stymied, but in the liver it is strongly upregulated. That may be because the liver tries to regenerate some mitochondria to try to potentially rescue some of the damage being done in muscle, he says.
An obvious next step, Beheshti says, is to study whether pharmaceutical therapies that are already approved to treat mitochondrial diseases or known nutritional interventions that support these organelles’ function might alleviate some of the negative effects of space radiation and antigravity.
“Mitochondria are well known to be exquisitely sensitive to environmental stresses such as high altitude, cold, and heat exposure,” says Adam Chicco, who studies mitochondrial physiology on Earth and in space at Colorado State University and was not involved in the new work. The new study supports their sensitivity to spaceflight as well and provides a “comprehensive blueprint” for investigating how mitochondrial responses might affect different body systems, Chicco says.