Sanders, I-Vt., has been sidelined since he was rushed to a hospital on Oct. 1, and the nearly three-hour showdown in Westerville, Ohio, will mark his return to the campaign. An audience of millions - including some wondering whether Sanders has the stamina for one of the world's most grueling jobs - is expected to tune in, and many of his supporters will be watching anxiously.
Sanders is not the only candidate facing high stakes, as this is the first debate since the impeachment inquiry into President Donald Trump jolted the Democratic race. Former vice president Joe Biden faces questions about his son's role in Ukraine, while Sen. Elizabeth Warren, D-Mass., has moved into first place in some polls, making her a newly tempting target, according to many Democrats.
But Sanders, 78, may have the most riding on the debate, sponsored by CNN and the New York Times, as scrutiny of his age and endurance are greater than at any point in his nearly half-century political career. A strong performance could help calm the doubts about his prospects as the oldest candidate in the field, while a weak showing could deal a devastating blow to a campaign that was already slipping.
"I certainly expect that there are a lot of people who will question his age - even more than that question may have been raised before," said Wayne Moynihan, a New Hampshire state representative who has endorsed Sanders. "It makes absolutely no difference to me, but I do recognize that it probably means something to someone else."
The senator from Vermont's performance has other implications for a fluid primary that has changed substantially since the last debate on Sept. 12. Both Biden and Warren would love to pull supporters away from Sanders, who has a loyal base of active devotees.
Over the weekend, Sanders hinted at his plans. His campaign announced he would hold his first rally since his heart attack on Saturday in New York City. And in an interview with ABC's "This Week with George Stephanopoulos," Sanders, who often brushes aside questions about his differences with Warren, noted that she identifies strongly as a capitalist and he does not.
All this makes it the most consequential debate so far, and it will feature a few wild cards. Billionaire climate activist Tom Steyer is making his debate debut. Rep. Tulsi Gabbard, D-Hawaii, has threatened to boycott the event. And with a dozen participants, it could become chaotic as candidates seek to break through the din.
"You have a lot of candidates on the stage with something to prove," said Democratic strategist Rebecca Katz. "Biden has to prove that he is the most electable. Bernie has to prove that he is in as good a shape as ever. And Warren has to not mess up."
For Sanders, the personal and political pressures of the past two weeks have been extraordinary. He was hospitalized in Las Vegas after experiencing chest pains at an Oct. 1 campaign event. Doctors inserted two stents to clear a blocked artery, though the campaign did not initially disclose that he'd suffered a heart attack.
Just days later, Sanders' daughter-in-law passed away from cancer at the age of 46. All this was happening after the senator was maintaining a breakneck campaign pace amid a growing threat from Warren's rise.
While Sanders is by nature a private person when he campaigns, he has opened up a bit since the heart attack. He released a seven-minute direct-to-camera video on Thursday that touched on his experience in the hospital while tying it to Medicare-for-all, an approach advisers hope Sanders continues.
Sen. Robert Casey Jr., D-Pa., a Biden supporter, said he recently spoke with Sanders. He wished Sanders a speedy recovery and the two discussed the death of his daughter-in-law, Casey recalled. Despite the tough circumstances, "he sounded great," Casey said.
On a conference call last week, Sanders thanked top campaign officials and told them to take care of their own health, according to Ben Cohen, co-founder of Ben & Jerry's ice cream, who serves as a Sanders campaign co-chair. Sanders said he plans to get back on the campaign trail and that his doctors predict a full recovery, Cohen said.
"I think the debate is an incredible opportunity for Bernie to reinvigorate his campaign," Cohen said in an interview. Others who have spoken with Sanders say the signature elements of his personality - dry humor, an interest in policy and a strong desire to campaign - are coming through.
It's unclear, though, whether Sanders will heed the advice of confidants who want him to publicly open up about his heart attack, at the debate and beyond. Before an earlier debate, advisers urged Sanders to sharply criticize Biden's relationship with his donors, but he shied away from a full-on attack. And at the campaign's outset, aides pressed Sanders to talk more about his personal story, but he soon dropped those efforts.
The bigger question may be whether following his heart attack, Sanders can convince enough primary voters that his age and health should not disqualify him from a hard-fought race against an aggressive Trump, let alone a job running the country. Many Democrats, while sympathizing with Sanders, suggested his physical well-being is reasonable for Democratic voters to consider.
"I feel terrible for Sen. Sanders. My heart goes out to him," said Steve Westly, a California investor who is fundraising for Biden. "But let's be honest: He's 78 years old. When you are that age, you really want to be looking vibrant, healthy. You just, you can't have people thinking you're old, tired, and likely to have serious health issues."
Westly added, "It's just hard to put a good spin on that one."
Yet Biden himself is 76. And questions about age and health might extend to candidates beyond Sanders on Tuesday, particularly Biden and Warren, who is 70. Like Sanders, they have agreed to release their health records before the first nominating contest in Iowa on Feb. 3.
Since he was discharged from the hospital, Sanders has repeatedly said he feels great. He has taken walks with his wife, Jane, and he played baseball with his grandchildren as he recuperated at home in Burlington, Vermont.
In an interview with CNN, Sanders said his cardiologist, whom he started seeing after his heart attack, said his recovery is going "very, very well." Asked how severe his heart attack was, Sanders would not answer directly, saying he was told that "we are on the road to a full recovery" and "within the next month, we'll see what happens."
His Democratic rivals have so far been diplomatic regarding Sanders's condition, wishing him a speedy recovery and voicing confidence he will bounce back. But they have been privately preparing to deal with potential questions from moderators about the subject on Tuesday night.
"What a tough time for him - genuinely," said Steyer, adding that he had called Sanders. "Between him having a health incident and then losing his daughter-in-law ... I think that must be so hard. And I really just wanted to send best wishes to him, and that's all I really did."
Asked whether an episode like a heart attack should factor into voters' choices, Steyer praised Sanders but did not answer directly.
Younger candidates pushing a message of generational change - such as South Bend, Indiana, Mayor Pete Buttigieg, 37, and former congressman Beto O'Rourke, 47 - will also appear onstage, creating the potential for a lively discussions of age.
"As the leader of the free world, it's arguably the most stressful job, and we have to make sure our candidate is ready," said Michael Tubbs, the mayor of Stockton, California. A Democrat who voted for Sanders in 2016 and is currently undecided, Tubbs said age and health are fair questions for all candidates. "You want your president there for all four years," he said.
Biden and Warren are likely to face scrutiny on other fronts during the debate, strategists said. Congressional Democrats have embarked on an impeachment inquiry following revelations that Trump pressed the president of Ukraine to investigate Biden and his son, Hunter Biden.
Trump and his allies have launched attacks on Biden that are unfounded but that some Democrats worry will nevertheless take a toll on his candidacy. And even some Democrats question why Hunter was serving on the board of a Ukrainian firm while his father was the Obama administration's point man on Ukraine. They wonder whether the furor will affect Biden's electability, which is his main appeal for many Democrats.
Biden, for his part, plans to challenge Trump in the debate, according to a person familiar with his strategy, and argue that the president is trying to handpick his 2020 opponent.
Warren has been steadily climbing in the polls, prompting more scrutiny of her left-leaning policies, including her support for Medicare-for-all and how it would affect middle-class taxes. Buttigieg called her explanation "extremely evasive" in a recent interview with CNN.
When it comes to Sanders, several of his prominent friends and supporters have advocated cutting back on his schedule when he plunges back into campaigning. Sanders, whose campaign calendar has been much fuller than most of his rivals', has sent mixed signals about what it will look like after Tuesday.
After initially telling reporters that "we're going to change the nature of the campaign a bit" by "probably not doing four rallies a day," Sanders reversed himself the next day, saying in an interview with NBC News that he "misspoke" and "said a word I should not have said." But the following day, he told to CNN that he probably will not be holding four rallies a day right away.
"I think for him and his family, yes, you'd like to see him hold fewer events because his message has gained traction without him," said Kelley Monahan, the register of deeds in Grafton County, New Hampshire, and a Sanders supporter.
Sanders' campaign has faced questions and criticism for waiting more than two days before revealing publicly that he had a heart attack, another subject that could come up at the debate. He and his campaign have defended the decision to disclose only limited information at first.
Perhaps above all else on Tuesday, it will be critical for Sanders to be self-assured, many Democrats say.
"To me, it's all about confidence," said Rufus Gifford, a former ambassador to Denmark who served as finance director on Barack Obama's 2012 campaign and has donated to some of Sanders' rivals. "If he's not a hundred percent on his game, it becomes more challenging for him."
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