Space travel syndrome: Bodily changes reflected in urine proteome following long-term flights

Space flight changes the body

The effects of weightlessness during space flight have been investigated for some time now, with several different parts of the body affected. When the astronauts return to Earth, many of the changes revert to normal in a few days, or possibly weeks, such as lowered respiratory rate, redistribution of body fluids and a decrease in muscle tissue.

Other changes are more serious. For instance, it is has already been established that astronauts aboard the Mir space station lost an average of 1-2% of bone mass each month, especially in the lower halves of their bodies. However, the changes varied widely between individual, with some losing up to 20% bone mass over 6 months of space flight.

In 2011, Russian scientists reported that when people were placed in a dry immersion bath to simulate weightlessness, irreversible changes occurred within just seven days, even when countermeasures such as myostimulation or mechanical stimulation were in place. Analysis of the proteins in serum pointed to changes in the inflammatory system, the immune system and in lipid metabolism.

Now, the same team of scientists has studied the urinary proteome of cosmonauts for the first time, comparing the protein composition before and after long-term space flight on the International Space Station. Researchers from the Yu. A. Gagarin State Scientific Research and Testing Cosmonaut Training Center, Star City, and the Institute of Biomedical Problems and the Emanuel Institute of Biochemical Physics, both at the Russian Academy of Science, Moscow, wanted to see if the physiological effects of factors like weightlessness, UV radiation, an artificial atmosphere and sleep disturbance were reflected by proteins in the urine.

Flight-induced changes in urinary proteins

Their subjects were six male cosmonauts who inhabited the ISS for 169-199 days before returning to Earth. Urine samples were collected before launch, then on the first and seventh days after landing. The proteins in each sample were separated using magnetic microparticles coated with a hydrophobic layer and deposited onto a target for analysis by matrix-assisted laser desorption/ionisation mass spectrometry. The samples were also analysed by LC-tandem MS to identify urinary peptides which might have appeared due to protein degradation.

The urine of all six cosmonauts contained no protein before flight, as measured by conventional urinalysis. However, proteins were found after landing, with the amounts decreasing over time. Of the 134 proteins identified in the mass range 1000-9900 Da, differences were observed for 31 proteins on the first day after landing, falling to nine proteins on the seventh day.

Peptides of various origins were also discovered in the urine before and after space flight. Most of them originated from blood plasma, representing peptides derived from cell death, cell membranes and structural proteins from connective tissue. Some of these appeared after flight whereas others disappeared, confirming that dynamic changes had occurred.

The team regarded those peptides which appeared after landing as the most important. They managed to identify 15 proteins from which the peptides were derived and they covered several functions. The majority originated from secreted proteins in the blood which came from the kidney, liver, bone marrow and blood cells. The remainder were intracellular and membrane proteins.

For two cosmonauts, small kidney stones (microliths) were detected under clinical examination, along with a short-lived increase in the level of creatinine. This observation correlated with an increase in the amount of the uromodulin in urine, which is associated with the progression of kidney disease and cell injury. The appearance of peptides related to granulins, which are immune response mediators, and alpha-1-antichymotrypsin, which is an acute-phase anti-inflammatory protein, illustrated the influence of multiple effects.

Liver damage was also implicated by clinical examination with enlarged livers, stagnation of the bile and hyperbilirubinemia found in some of the men. Increases of the enzyme L-lactate dehydrogenase B-chain in the urine could be a signal of this damage.

For all six cosmonauts, the occurrence of peptides derived from the extracellular matrix pointed to its degradation during long flights. The appearance of urinary proteins with protease-antiprotease activity supports the occurrence of protein degradation during post-flight readaptation.

So, several clinical effects have been implicated by the proteomic analysis of cosmonaut urine, suggesting that this is a viable method for detecting and monitoring changes in the body following prolonged space flight. Studies of this type are necessary to predict how humans will react to even longer flights, such as extended stays on the ISS or flights to Mars, which will take about two years.