The Yankees lost a series finale to the Orioles on Wednesday night for many reasons, and here are three big ones: 1) Brett Gardner did not start again, 2) Chase Headley threw inaccurately again and 3) Dellin Betances was unavailable.

If those issues were isolated, no big deal, move along, nothing to see here.

But the fragility of Gardner and Jacoby Ellsbury, the throwing uncertainties of Headley and the heavy workloads endured by Betances and Andrew Miller have been issues that have loomed over this Yankee season, likely will be factors down the stretch and — here is a key matter — will not exactly go away when this Yankees season concludes.

These are players the Yankees are invested in and are building around for the future. What does that mean?

Gardner/Ellsbury

When right, the duo gives the Yankees a dynamic 1-2 combo atop the lineup and in left and center field. But what makes them valuable — their athleticism and physicality — also breaks them down over the course of the season.

Ellsbury turns 32 Friday, the same age as Gardner. That increases the likelihood of their agility diminishing while their fragility rises.

Ellsbury’s injury history is the large bugaboo on his résumé, and he missed another seven weeks this season with a sprained knee. He has five years at just less than $111 million remaining after this season and it is very possible his contract — because of the combination of length left and his physical withering — could be viewed as the Yanks’ greatest financial albatross because the deals for Alex Rodriguez, CC Sabathia and Mark Teixeira all expire by the end of 2017, at the latest.

Gardner has proven far more durable than Ellsbury, but that durability and his all-out style lead to erosion. His worst months last year were August and September. This season he had an .835 OPS through July 31 and .551 since — among players with 125 plate appearances since Aug. 1, that is the fifth worst. He was set to return to the lineup Thursday night (before the game against Toronto was postponed) after not starting the three previous games due to a shoulder injury incurred running into an outfield wall.

Joe Girardi said in acknowledgment of their styles he tries never to play Gardner or Ellsbury more than 10 or 11 days in a row. But even that might have to be modified as they age (Gardner has two years at $25 million left after this season).

In Slade Heathcott and Mason Williams, the Yanks have players with similar skill sets to Ellsbury/Gardner; and the Yanks particularly believe Williams turned a maturity corner this year and has a high upside. Perhaps one will make the team next year to give Girardi an option to lessen the physical toll on his starters.

Headley

There was a team interested in Headley as a free agent last offseason that passed, in part, because it believed he had developed the yips. Yankees bench coach Rob Thomson insists Headley does not have the yips, but rather has a tendency to “not be in sync” with his feet and hands. “He’s come out of [having the problem] and gone back into it at times,” Thomson said.

Headley was not charged with an error Wednesday when he threw something akin to a screwball that Stephen Drew flubbed. Then again Headley has been spared a bunch of errors this season by the scoops of Teixeira and even Greg Bird. Still, his 20 errors led major league third basemen and his 10 on throws were second most, surprisingly to Toronto’s Josh Donaldson, who is considered an ace defender.

The Yanks do not have another third baseman ready to play, and even if they did, they still owe Headley $39 million over three years. Thomson raved about Headley’s work ethic, and believes the switch hitter will overcome the problem. He must. Because unlike the MVP-ish Donaldson, Headley’s league-average offense makes any defensive deficiencies more glaring.

Betances/Miller

The Yankees believed they had built a team bullpen, but part of the use (overuse?) of Betances and Miller is associated with shakiness elsewhere in the pen, notably in several games in which the Yanks were steadily blowing big leads. Girardi just will not surrender a sure win, and has gone to Betances and Miller to avert crisis.

To date, Girardi has not used either guy on more than two consecutive days. But Betances has thrown the second-most relief pitches this season and the most over the last two years.

Betances and Miller are the Yankees’ best weapon, and Girardi is daily faced with how much to deploy them without wearing them out.

It is why the Yankees considered giving up arguably their best prospect, Single-A shortstop Jorge Mateo, in a trade for San Diego’s Craig Kimbrel in July. It would not be surprising to see the Yankees use the offseason to pursue Kimbrel or another standout reliever as a way to share the innings/burden with Betances/Miller.