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After 355 days aboard the ISS, NASA astronaut and five-time flight engineer Mark T Vande Hei returns to Earth as record holder for the longest single spaceflight in NASA history, having surpassed Commander Scott Kelly’s 340-day mark set in 2018. Though not as long as Peggy Whitson’s 665 cumulative days spent in microgravity, Vande Hei’s accomplishment is still one of the longest single stints in human spaceflight, just behind Russia’s Valeri Polyakov, who was aboard the Mir for 438 straight days (that’s more than 14 months) back in the mid-1990s.

Though NASA’s Human Research Program has spent 50 years studying the effects that microgravity and the rigors of spaceflight have on the human body, the full impact of long-duration space travel has yet to be exhaustively researched. As humanity’s expansion into space accelerates in the coming decades, more people will be going into orbit — and much farther — both more regularly and for longer than anyone has in the past half century, and they’ll invariably need medical care while they’re out there. To fill that need, academic institutes like the Center for Space Medicine at the Baylor College of Medicine in Houston, TX, have begun training a new generation of medical practitioners with the skills necessary to keep tomorrow’s commercial astronauts alive on the job.

Even traveling the relatively short 248-mile distance to the International Space Station does a number on the human body. The sustained force generated during liftoff can hit 3 gs, though “the most important factors in determining the effects the sustained acceleration will have on the human body is the rate of onset and the peak sustained g force,” Dr. Eric Jackson wrote in his 2017 dissertation, An Investigation of the Effects of Sustained G-Forces on the Human Body During Suborbital Spaceflight. “The rate of onset, or how fast the body accelerates, dictates the ability to remain conscious, with a faster rate of onset leading to a lower g-force threshold.”

Untrained civilians will begin feeling these effects at 3 to 4 gs but with practice, seasoned astronauts using support equipment like high-g suits can resist the effects until around 8 or 9 gs, however the unprotected human body can only withstand about 5 gs of persistent force before blacking out.

Once the primary and secondary rocket stages have been expended, the pleasantness of the spaceflight will improve immensely, albeit temporarily. As NASA veteran with 230 cumulative days in space, Leroy Chiao, told Space in 2016, as soon as the main engines cut out, the crushing Gs subside and “you are instantly weightless. It feels as if you suddenly did a forward roll on a gym mat, as your brain struggles to understand the odd signals coming from your balance system.”

“Dizziness is the result, and this can again cause some nausea,” he continued. “You also feel immediate pressure in your head, as if you were lying down head first on an incline. At this point, because gravity is no longer pulling fluid into your lower extremities, it rises into your torso. Over the next few days, your body will eliminate about two liters of water to compensate, and your brain learns to ignore your balance system. Your body equilibrates with the environment over the next several weeks.”

Roughly half of people who have traveled into orbit to date have experienced this phenomenon, which has been dubbed Space Adaptation Syndrome (SAS), though as Chiao noted, the status debuffs do lessen as the astronaut’s vestibular system readjusts to their weightless environment. And even as the astronaut adapts to function in their new microgravity surroundings, their body is undergoing fundamental changes that will not abate, at least until they head back down the gravity well.

“After a long-duration flight of six or more months, the symptoms are somewhat more intense,” Chiao said. “If you've been on a short flight, you feel better after a day or two. But after a long flight, it usually takes a week, or several, before you feel like you're back to normal.”

“Spaceflight is draining because you've taken away a lot of the physical stimulus the body would have on an everyday basis,” Dr. Jennifer Fogarty from Baylor’s Center for Space Medicine, told Engadget.

“Cells can convert mechanical inputs into biochemical signals, initiating downstream signaling cascades in a process known as mechanotransduction,” researchers from the University of Siena noted in their 2021 study, The Effect of Space Travel on Bone Metabolism. “Therefore, any changes in mechanical loading, for example, those associated with microgravity, can consequently influence cell functionality and tissue homeostasis, leading to altered physiological conditions.”

Without those sensory inputs and environmental stressors that would normally prompt the body to maintain its current level of fitness, our muscles will atrophy — up to 40 percent of their mass, depending on the length for the mission — while our bones can lose their mineral density at a rate of 1 to 2 percent every month.

"Your bones are … being continually eaten away and replenished," pioneering Canadian astronaut Bjarni Tryggvason told CBC in 2013. "The replenishment depends on the actual stresses in your bones and it's mainly … bones in your legs where the stresses are all of a sudden reduced [in space] that you see the major bone loss.”

This leaves astronauts highly susceptible to breaks, as well as kidney stones, upon their return to Earth and generally require two months of recovery for every month spent in microgravity. In fact, a 2000 study found that the bone loss from six months in space “parallels that experienced by elderly men and women over a decade of aging on Earth.” Even intensive daily sessions with the treadmill, cycle ergometer and ARED (Advanced Resistance Exercise Device) aboard the ISS, paired with a balanced nutrient-rich diet, has only shown to be partially effective at offsetting the incurred mineral losses.

And then there’s the space anemia. According to a study published in the journal, Nature Medicine, the bodies of astronauts appear to destroy their red blood cells faster while in space than they would here on Earth. "Space anemia has consistently been reported when astronauts returned to Earth since the first space missions, but we didn't know why," study author Guy Trudel said in a January 14 statement. “Our study shows that upon arriving in space, more red blood cells are destroyed, and this continues for the entire duration of the astronaut’s mission.”

This is not a short term adaptation as previously believed, the study found. The human body on Earth will produce and destroy around 2 million red blood cells every second. However, that number jumps to roughly 3 million per second while in space, a 54 percent increase that researchers attribute to fluid shifts in the body as it adapts to weightlessness.

Recent research also suggests that our brains are actively “rewiring” themselves in order to adapt to microgravity. A study published in Frontiers in Neural Circuits investigated structural changes found in white matter, which interfaces the brain’s two hemispheres, after space travel using MRI data collected from a dozen Cosmonauts before and after their stays aboard the ISS, for about 172 days apiece. Researchers discovered changes in the neural connections between different motor areas within the brain as well as changes to the shape of the corpus callosum, the part of the brain that connects and interfaces the two hemispheres, again due to fluid shifts.

"These findings give us additional pieces of the entire puzzle," study author Floris Wuyts of Floris Wuyts, University of Antwerp told Space. "Since this research is so pioneering, we don't know how the whole puzzle will look yet. These results contribute to our overall understanding of what's going on in the brains of space travelers."

As the transition towards commercial space flight accelerates and the orbital economy further opens for business, opportunities to advance space medicine increase as well. Fogarty points out that government space flight programs and installations are severely limited in the number of astronauts they can handle simultaneously — the ISS holds a whopping seven people at a time — which translates into multi-year long queues for astronauts waiting to go into space. Commercial ventures like Orbital Reef will shorten those waits by expanding the number of space-based positions available which will give institutions like the Center for Space Medicine more, and more diversified, health data to analyze.

“The diversity of the types of people that are capable and willing to go [into space for work] really opens up this aperture on understanding humanity,” Fogarty said, “versus the [existing] select population that we always struggle to match to or interpret data from.”

Even returning from space is fraught with physiological peril. Dr. Fogarty points out that while in space the gyroscopic organs in the inner ear will adapt to the new environment, which is what helps alleviate the symptoms of SAS. However, that adaptation works against the astronaut when they return to full gravity — especially the chaotic forces present during reentry — they can be shocked by the sudden return of amplified sensory information. It’s roughly equivalent, she describes, to continuing to turn up the volume on a stereo with a wonky input port: You hear nothing as you rotate the knob, right up until the moment the input’s plug wiggles just enough to connect and you blow your eardrums out because you’d dialed up the volume to 11 without realizing it.

“Your brain has acclimated to an environment, and very quickly,” Fogarty said. “But the organ systems in your ear haven't caught up to the new environment.” These effects, like SAS, are temporary and do not appear to limit the amount of times an astronaut can venture up to orbit and return. “There's really no evidence to say that we would know there would be a limit,” she said, envisioning it could end up being more of a personal choice in deciding if the after-effects and recovery times are worth it for your next trip to space.