After spending 340 days in space, U.S. astronaut Scott Kelly and Russian cosmonaut Mikhail Kornienko are scheduled to touch down on our little blue marble around 11:30 p.m. ET today.

Though not the longest stint in space, it is the longest anyone has spent on board the International Space Station (ISS) and the best opportunity NASA has had to study what happens to the human body after prolonged exposure to weightlessness, cramped quarters and damaging radiation.

There’s no escaping the fact that Earthlings evolved to thrive with a certain amount of gravity. So since the early days of space travel, NASA has been trying to figure out what happens to a human body beyond our planet's pull.

“All those normal things that we take for granted, nobody was sure quite what would happen,” says Valerie Neal, curator and chair of space history at the Smithsonian National Air and Space Museum. “Will they be able to swallow properly? Will they be able to see properly? Will they be able to urinate?”

The earliest experiments were done with animal subjects—dogs, monkeys and mice, to name a few. Then in 1962, astronaut John Glenn became the first American to orbit Earth, along with a tube of applesauce.

“They picked a nice soft, slippery food and put it in a toothpaste tube and had him take just little bits at a time to see if he could swallow and if the food would move down to his stomach,” says Neal. But the short duration of these flights limited what scientists could test—and tested the patience of the pioneering space travelers. “Astronauts were so busy doing what they needed to do, and they weren’t necessarily inclined to be treated as guinea pigs,” Neal adds.

As the length of flights increased, so did physiology testing. These days, ISS astronauts are exposed to a battery of tests before flight, regular health checks in-flight and a lengthy rehabilitation once their feet return to firm ground.

But with their sights on Mars, NASA still has much to learn about the effects of longer treks. For Kelly and Kornienko, their "Year in Space" mission is the first to focus solely on the physiology of being in space—a project made even more intriguing because Kelly has a twin brother on Earth. That means scientists will be able to look at both men and better identify any genetic changes caused by spaceflight.

Though we likely will learn much more from Kelly and Kornienko in the coming months, here are a few of the big effects NASA will be looking out for:

Spinning Heads Over Tails

Your inner ear works roughly like an accelerometer in a smartphone—it tells your body when you are moving or stopped, and when you are standing on your head or lying on your side. But in space, that little mechanism goes awry, which often gives astronauts motion sickness for a day or so after entering microgravity. Many also experience a similar problem when re-entering our planet’s pull, says Neal.

“It’s like coming off a ship and not having your land legs under you,” she says. Astronauts often initially report a sense of floating that eventually dissipates as their bodies re-adjust to Earth.

Bones and Muscles

One of the first things that scientists discovered in our ventures into space is that the low-gravity lifestyle doesn’t lend itself to strong bones and muscles, including the heart. While Earth-bound, these body parts actually work a fair amount just to keep us standing still. Without the downward force of gravity, the body works considerably less, causing muscle deterioration and loss of bone density.

In a single month in space, astronauts can lose as much bone mass as a postmenopausal woman does in a year, according to NASA. This startling decrease causes higher calcium levels in the blood, which can lead to a greater incidence of renal stones. To counteract these problems, astronauts exercise vigorously using specially designed machines aboard the space station. Kelly has exercised roughly 700 hours throughout the course of his mission, according to NASA.

Most of these effects can be counteracted upon landing, but it does take some work. “Just holding my head up is a bizarre new experience," astronaut Chris Hadfield told CBC News after a stint on the ISS in 2013. “I haven’t had to hold my head on top of my neck for five months.”

Floating Fluids

Every second, fluids rush throughout our bodies, and for the Earth-bound, gravity helps move these fluids down into the legs. But take away gravity, and the fluids float up to the head. According to NASA, over the course of his year in space, the amount of fluid shifting into Scott Kelly’s head could fill a two-liter soda bottle.

Because of this, the astronauts “tend to look cheekier,” says Neal. This fluidic drift also causes more serious conditions, including pressure on the optic nerve, which can affect vision. Once back on Earth, the eye troubles usually subside, but this is one of the big issues NASA wants to understand for longer-duration flights.

Cosmic Radiation

Earth's magnetic field provides a form of natural shielding that protects life on the surface from a good amount of high-energy radiation, which could otherwise damage DNA. Outside this safe zone, artificial shielding on the ISS can partially protect astronauts from radiation exposure, but it isn’t effective for all radiation types, leaving astronauts more susceptible to cancer and other long-term health risks.

A trip to Mars will be even more brutal, because in addition to the exposure time in transit, the red planet has no natural magnetic shield. With the latest ISS mission, scientists are hoping to suss out exactly how space radiation might trigger changes in Kelly’s DNA, and what that might mean for future Mars-bound travelers.

Despite all these severe-sounding effects, most of the known damage can be reversed after an astronaut’s return to Earth. In a press conference from space last week, Kelly was in high spirits. Though he reports some minor effects to his eyes, he says overall that he feels well and is in good shape psychologically: “It’s not like I’m climbing the walls.”

“I’ve tried to do this with a very deliberate methodology and deliberate pace,” he says, adding that he has used each mission task as a milestone. “I think that’s important, having those kinds of milestones that break up a long-distance flight. The next milestone is coming home.”