Brian O'Driscoll starts Saturday's RBS 6 Nations clash with Wales at outside centre, while fellow Test centurion Ronan O'Gara has been selected on the bench for the all-Celtic showdown at the Millennium Stadium. Paul O'Connell, the third member of the squad's distinguished senior trio, has been ruled out of the championship with a back injury.
Harlequins director of rugby O'Shea - who won 35 caps for Ireland between 1993-2000 - believes that when they do retire, the leadership void must be filled by Jamie Heaslip and Rob Kearney, and he said: "People are talking about life after the three 'Os' - O'Driscoll, O'Gara and O'Connell - but there's still some life in the old dogs yet."
He added: "They will be coming to an end in the next year or two, however, and they have to be replaced by people like Jamie Heaslip and Rob Kearney."
O'Shea is convinced that Ireland can make an impact in the Six Nations following a mixed autumn that ended with a record victory over Argentina.
"If you add players like Rob Kearney and Luke Fitzgerald, who are fit again, into the mix of the team that played against Argentina, you've got a competitive side," he said. "Ireland can be a threat. Though they lost fairly convincingly in the third Test in New Zealand over the summer, they came within two minutes of winning the second Test.
"They had a good lead going into the second half against South Africa in the autumn but were overpowered.
"Munster second row Donnacha Ryan is stepping forward as a potential Lions lock and you have players who are coming into the team. Craig Gilroy scored a great try against Argentina and looks electric."
O'Shea has identified England's clash with France at Twickenham on February 23 as the championship's pivotal encounter, though doubts any team will win the Grand Slam this year.
"There are four teams that, if they get on a roll, can win the Six Nations, but I don't see a Grand Slam this year because it's so incredibly competitive between those four," he said. "France and England are right up there at the moment as favourites, with Ireland and Wales both very capable and following closely behind."