Okay, so at this point:
- Ned's wife Maude is canonically dead.
- Apu, his wife, and his brother are gone from the show.
- Edna is canonically dead after her VA died.
- Lionel Hutz and Troy McClure are gone after their VA died.
- Milhouse is either gone from the show or won't have his iconic voice. Possibly Jimbo too, although I think his voice could reasonably be replaced. Not sure about Rod.
- The larynx of Marge's VA, age 74, is on its last legs. The other VAs for the family are in their 60s.
- The VA for Flanders, Skinner, Reverend Lovejoy, Mr. Burns, Smithers, and Kent Brockman is 80.
- The show has had new episodes (774 of them) being put out since 1989.
- The show is in its analog to the SpongeBob meta/dead cat bounce era, where it's recovered from being abysmal and is now just kind of watchable.
- The overwhelming majority(?) of the original writers are gone.
- The show has jumped the shark like 50 times.
- The satire has literally no bite.
Just put it out of its misery already. Jesus christ.
Edit: I can't imagine too how many VAs died or retired accounting for dubs in different languages.