TOKYO -- As the Mariners prepare to open the 43rd season in franchise history, seemingly more questions loom than ever regarding a club that made an unusually large number of moves to make over its roster this past offseason.

With so many familiar faces gone, the Mariners have a chance to start from a clean slate this season. But that means there are more uncertainties than usual, given the number of newcomers, as well as a plan by general manager Jerry Dipoto aimed toward better contending in a year or two once an improved flock of prospects matures enough to contribute.

So what should we expect this season, which gets underway Wednesday, when Seattle faces Oakland in a 2:35 a.m. PT opener at the Tokyo Dome?

Here are five keys to the Mariners' season:

1. Who steps up?

Last year featured breakout seasons by Mitch Haniger and Marco Gonzales, who now find themselves the nucleus of a youth movement that won’t fully arrive until next season. But Dipoto added a group of new players who have had a taste of the Majors and could be ready to solidify their own futures.

New left-hander Yusei Kikuchi appears the most-likely candidate to insert himself as a big-time piece of the puzzle, and it seems only a matter of time before 22-year-old Justus Sheffield -- another southpaw -- gets his opportunity to show why he’s Seattle's No. 1-ranked prospect following his acquisition from the Yankees in the James Paxton trade.

Left fielder Domingo Santana had his breakout season two years ago when he hit .278 with 30 homers and 85 RBIs for the Brewers, but he struggled last year and now has a chance to re-establish his career with Seattle. Center fielder Mallex Smith did his bust-out routine last season, when he hit .298 and stole 40 bases with the Rays, but if the 25-year-old can follow that up this year, it would go a long way toward cementing his place in the Mariners' plans.

2. How well and how long do the veterans play?

For all the talk of rebuilding, the Mariners remain in a state of transition since veterans like Felix Hernandez, Edwin Encarnacion, Jay Bruce, Kyle Seager, Dee Gordon and Mike Leake are still on the team. Add in Ichiro -- who’ll at least start the regular-season with the club in Japan -- that’s seven players who have a combined 82 seasons, 25 All-Star berths and $110 million in salary this year.

But Hernandez and Encarnacion are in the final years of their contracts. And should any of this group play well enough to raise their trade value by midseason, Dipoto will be shopping them for younger players who better fit the long-term window.

The irony, of course, is if some of those veterans play well, the second half of the season for Seattle could become more of a struggle after the Trade Deadline if Dipoto goes into full-scale sell mode, as expected.

3. Can the nucleus stay healthy?

Seager has already been lost for about three months following surgery to repair a tendon in his left hand. Smith missed all of camp with a strained right elbow, though he could be ready by the time the club returns to Seattle. But this isn’t a team with enough depth to withstand a rash of injuries, which is true of most MLB teams.

The pitching rotation stayed relatively healthy last year, which is a rarity. There is some new depth there with prospects Sheffield and Erik Swanson and veteran lefty Tommy Milone, but an injury bug like the one that bit the rotation two years ago would make this season very difficult, and that has already arisen in the bullpen, where Shawn Armstrong, Gerson Bautista, Anthony Swarzak and Sam Tuivailala are all opening the year on the injury list

4. Is any relief in sight?

Bullpen’s are almost always the most volatile and unpredictable component of any roster, and that is particularly true with these Mariners after Dipoto dealt Edwin Diaz, Alex Colome, Juan Nicasio, James Pazos and others. Outside of free-agent closer Hunter Strickland, the Mariners have almost no proven late-inning relievers, a point that became strikingly noticeable when Strickland missed more than a week with a sore back late in camp.

Dan Altavilla, Cory Gearrin, Chasen Bradford and Zac Rosscup are going to get opportunities to step up, and more help will eventually be on the way when the injured players start returning. But this will be an interesting situation to watch all season.

5. Defense, defense, defense

New infield coach Perry Hill is one of the best in the game, and he’ll be put to the test, particularly with Seager sidelined nearly half the season. Ryon Healy can play third, but not at Seager’s level. Shortstop Tim Beckham and the first base/designated hitter group of Encarnacion, Bruce and Daniel Vogelbach aren’t renowned for their glove work either.

Add in the fact that catcher Omar Narvaez is a capable hitter, but a work-in-progress behind the plate, and this figures as a critical area. The Mariners won a ton of close games last year with a strong bullpen and solid defense. This year's lineup looks capable of putting up runs, but run prevention is going to be key as well.