John McCain will be an 80-year-old senator if he wins re-election to a sixth term.  But the octogenarian senator has far more to deal with than questions about his age.

Several conservative PACs have already targeted McCain for defeat, notably the Senate Conservative Fund and the Club for Growth.  With the right sharpening its knives to bring him down, the question of his survival in a Republican primary can't be dismissed.

The Hill:

“There are few Republicans who have betrayed our conservative principles more than John McCain,” SCF President Ken Cuccinelli said in an email to supporters Tuesday of the party's 2008 nominee for president. 

“John McCain lost his way a long time ago and it's time to replace him with a strong conservative leader who will support and defend the Constitution.” 

Cuccinelli’s email links to a petition to replace McCain, which, as of 2 p.m. ET, has 457 signatures. He slams McCain for high-profile instances where he crossed the aisle, including helping to forge the bipartisan Senate immigration bill, as well as voting for various fiscal cliff and debt limit deals. 

McCain is set to announce his decision to run again during a speech at an Arizona Chamber of Commerce luncheon in Phoenix. He teased the decision in an interview with NBC News posted late Monday night.

"I'm ready. I am more than ready. In some ways, I am eager,” he told NBC’s Kelly O’Donnell. “I think I have the knowledge and background to help the nation through very perilous times, and I believe that I can still contribute in many ways to the welfare and benefit of my state.”

The SCF isn’t the first conservative group to target McCain. The president of the Club for Growth said the group might support a primary challenger to the five-term senator. And Reps. David Schweikert and Matt Salmon (R-Ariz.) both told The Hill in February that they’re eyeing a bid to unseat McCain.  

McCain was once the standard-bearer of the party during his run for president. He struggled at times with the party’s base during the primaries, mainly over his immigration position.  

Conservatives believe there is far more to complain about with McCain than his stance on immigration.  He has demonstrated overt hostility to the right since his defeat in 2008.  And along with South Carolina senator Lindsey Graham, he has frequently been at odds with conservatives over judges, administration nominees, and budget issues.

He beat back a strong primary challenge in 2010 from Rep. J.D. Hayworth while cruising to victory in the general election.

Will he be as lucky this time? 

Unless Arizona Republicans nominate a whack-job for the Senate, the seat is fairly safe no matter who runs.  If Arizona Republicans can be convinced that McCain has outlived his usefulness and that a solid conservative replacement can do the job, McCain – like Lugar and Bennett before him – will be retired.