Whitson will be 56 when she rockets off the planet Thursday. She'll celebrate her 57th birthday in February on the International Space Station.
That's a far cry from John Glenn's space shuttle flight at age 77 and a few years shy of the male runners-up. But it's enough to beat Barbara Morgan's record as the world's oldest spacewoman. Morgan waited so long to fulfill her role as Christa McAuliffe's teacher-in-space backup that she was 55 when she finally flew in 2007.
"I love working at NASA, but the part that has been the most satisfying on a day-to-day basis, hour-to-hour, minute-to-minute, has been working on board the space station," Whitson told reporters over the summer.
"It doesn't matter if I'm cleaning the filters. I feel like I'm helping personally push forward exploration. ... that's the why I want to go again."
Strict when it comes to lifetime radiation exposure, NASA insisted Whitson remain Earth-bound for a while after her 2008 mission.
Whitson was the first woman to serve as commander of the space station - in 2007, nine years into its lifetime. She also was the first - and so far only - woman to head NASA's male-dominated astronaut corps. No other woman has spent more time in space.
She'll ride a Soyuz rocket with a Russian cosmonaut, Oleg Novitskiy, 45, and a French newcomer to space, Thomas Pesquet, who's 38. The launch is 3:20 p.M. EST Thursday, 2:20 a.M. Friday in Kazakhstan.
A French documentary crew followed Pesquet during training, focusing on his relative youth and fresh eyes. Whitson said the interest on her, by comparison, was for being "old and experienced."
Her biochemist husband, Clarence Sams, also works for NASA.
Whitson already has spent 377 days in space and performed multiple spacewalks. Her upcoming six-month mission should push her beyond 534 days in space, the U.S. Record set in September by 58-year-old astronaut Jeffrey Williams.
Whitson said she's had a lucky run with few regrets. But she noted: "In terms of goals for NASA before I die, we need to be living on Mars.
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