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WASHINGTON—Sen. Richard Shelby (R., Ala.), the top Republican on the Appropriations Committee, said Monday he wouldn’t run for re-election next year.

Mr. Shelby, 86 years old, is currently serving his sixth term in the Senate. He is the latest in a string of Senate Republicans to announce that they don’t plan to run for re-election in 2022, joining Sens. Richard Burr of North Carolina, Pat Toomey of Pennsylvania and Rob Portman of Ohio.

The senior Republicans have played leadership roles in the major tax and spending legislation produced by Congress.

While Republicans are expected to retain Mr. Shelby’s seat in Alabama, the seats in Pennsylvania and Ohio are expected to be competitive, given that Democrats hold one seat apiece in those two states. North Carolina also has played host to tight races in recent elections.

So far, no Democrats up for re-election have announced their retirements. The party split in the Democratic-controlled Senate is currently 50-50, with Vice President Kamala Harris able to break any ties.