He told CNN, "You could say that, after this, it is a bit late to reform the EU. Clearly, for a lot of people, not just British, the EU is seen as being part of the problem, not the solution.
"This is very worrying. We now need a revamped EU model and that is the collective responsibility of the European political class."
Former European trade Commissioner Peter Mandelson painted a grim picture for the future of the UK, saying its economy will be "dogged for years by uncertainty."
The Socialist veteran told BBC News, "As a society, we will become more polarised and divided and the country will become poorer. For business, this outcome is a killer and the ramifications will go on for years."
He also called the vote a "calamity" for Northern and Southern Ireland.
London Mayor Sadiq Khan sought to reassure the business community that "London remains open for business" and that the UK will continue to trade with Europe and the rest of the world.
Labour leader Jeremy Corbyn, facing calls to quit over what some saw as his lacklustre support for Remain, warned of "difficult days ahead" and possible "job consequences."
It is reported 55 Labour MPs have signed a letter calling for Corbyn to quit.
UKIP's Nigel Farage called for a "Brexit government" and for the UK to immediately start trade negotiations with the EU.
Farage said the result was partly the result of Labour voters rejecting the Remain call by the party's leadership.
US presidential candidate Donald Trump, arriving in the north of Scotland to visit his new golf complex on Friday, described the result as "fantastic."
Meanwhile, Sinn Fein has now called for a referendum on possible reunification with southern Ireland. Similar calls were made by Scottish nationalists for an independence referendum there.
Europe's far-right parties hailed the UK's vote to leave as a victory for their own anti-immigrant and anti-EU stance and vowed to push for similar referendums in their own countries.
France's Front National (FN) saw it as a clear boost for Marine Le Pen's presidential bid next year and momentum for the party's anti-Europe and anti-immigration line.
Le Pen told RTL radio: "Like a lot of French people, I'm very happy that the British people held on and made the right choice. What we thought was impossible yesterday has now become possible."
The Dutch far-right and anti-immigration leader Geert Wilders called on Friday for a referendum on the Netherlands' membership of the European Union.
"I think it's historic," he told Dutch radio. "I think it could also have huge consequences for the Netherlands and the rest of Europe. Now it's our turn. I think the Dutch people must now be given the chance to have their say in a referendum."
In Germany, Beatrix von Storch, an MEP for right-wing populist party Alternative für Deutschland, who was recently expelled from the Tories' party group in the European Parliament over her "shooting refugees" comments, welcomed the result.
"23 June is a historic day. It is Great Britain's independence day. The people were asked - and they decided. The EU as a political union has failed."
The leader of Italy's far-right Northern League party was swift to celebrate the Brexit outcome. "Hurrah for the courage of free citizens! Heart, head and pride beat lies, threats and blackmail. Thanks UK, now it's our turn," said Matteo Salvini, whose popularity has increased in recent years on the back of an anti-EU, anti-immigration platform.
Norbert Hofer of Austria's right wing populist Freedom Party, who narrowly lost out on his country's presidency last month, tweeted: "UK votes to leave! In the coming days we will recognise the full significance of this decision."