“Perhaps in the Democratic primary and certainly in the general election, there’s going to be an argument that the time for a change of leadership has come,” said the Republican strategist Karl Rove. “The idea that we’re at the end of her generation and that it’s time for another to step forward is certainly going to be compelling.”

A yesterday-versus-tomorrow argument against a woman who could be the last major-party presidential nominee from the onset of the baby boom generation would be a historically rich turnabout. It was Mrs. Clinton’s husband, then a 46-year-old Arkansas governor, who in 1992 put a fellow young Southerner on the Democratic ticket and implicitly cast the first President George Bush as a cold war relic, ill equipped to address the challenges of a new day. Mr. Clinton then did much the same to Bob Dole, a former senator and World War II veteran, in 1996.

A Republican approach that calls attention to Mrs. Clinton’s age is not without peril, and Democrats predict that it could backfire.

“They would go to that place at their own risk,” said Representative Nancy Pelosi of California, the Democratic minority leader and first female speaker, noting that “Age is like art — it’s a matter of interpretation.”