Mikhail Kornienko and Scott Kelly are to spend 342 days aboard the orbiting laboratory, about twice as long as a standard mission on the station. Russia's Gennady Padalka is beginning a six-month stay.
The three astronauts entered the station about eight hours after launching from Russia's manned space facility in Kazakhstan. They were embraced by American Terry Virts and Russia's Anton Shkaplerov who along with Italian Samantha Cristoforetti have been aboard since late November.
The stay is aimed at measuring the effects of a prolonged period of weightlessness on the human body, a step toward possible missions to Mars or beyond.
Kelly's identical twin Mark, a retired astronaut, agreed to take part in many of the same medical experiments as his orbiting sibling to help scientists see how a body in space compares with its genetic double on Earth. They are 51.
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Kelly and Kornienko, 54, will remain on board until next March. During that time, they will undergo extensive medical experiments, and prepare the station for the anticipated 2017 arrival of new US commercial crew capsules. That means a series of spacewalks for Kelly, which will be his first.
Doctors are eager to learn what happens to Kelly and Kornienko once they surpass the usual six-month stay for space station residents.
Bones and muscles weaken in weightlessness, as does the immune system. Body fluids also shift into the head when gravity is absent, putting pressure on the brain and the eyes, impairing vision for some astronauts in space.
The yearlong stint will allow doctors to assess whether such conditions are aggravated by a long spell in space or whether they reach a point of stasis or even taper off.
Last year, as tensions between Russia and the United States grew amid the dispute over Russia's role in Ukraine, Deputy Prime Minister Dmitry Rogozin had said Moscow aimed to exit the project in 2020.