There's a lot of uncertainty at all levels, mainly because we've never had a manned structure in space for this long. Mir set the previous record at 15 years. The ISS reached that milestone in 2013. We've already found that the station lasts longer than its initial design life (PDF, page 3):
In November 2013, the International Space Station (ISS or Station) completed 15 years of continuous operation in low Earth orbit, marking a significant achievement in the history of human spaceflight. Two months later, the Administration announced its intent to extend Station operations until 2024. Originally designed and tested for a 15-year life span, the ISS may now operate for 26 years.
At one point, NASA was working on certifying the station for use until 2028:
Hardware Assessment and Certification. NASA and its international partners designed and tested the ISS for a 15-year life span – a benchmark the oldest segments of the Station surpassed in November 2013. The NASA Authorization Act of 2010 extended the life of the Station until 2020, and NASA and its Canadian, Japanese, and European partners have certified that the ISS structure and hardware are sufficient to continue operations until that date.16 In January 2014, the President announced his support for extending Station operations until at least 2024.17 Prior to this announcement, NASA had initiated a feasibility assessment for continuing operations until 2028. (NASA defines an assessment as the method for performing verification or certification. For ISS certification, the focus is primarily on analytical assessments using the performance data from the 15 years of ISS operation. NASA expects to complete its 2028 assessment in 2018.)
Investigations into extending ISS lifespan to 2028 started in 2010.
There are several components that are seen as 'most likely to cause trouble':
- the hardware that attaches the truss to the pressurized modules.
- high-pressure oxygen lines
- solar panels (power levels are dropping faster than expected)
- EPROMs that lose their stored data
Then there are things like the seals between modules that would be difficult to replace if they failed.
So at some point, there are components you need to replace (in some cases, in a very expensive operation) before they fail. Then prolonging the life of the station becomes a political and budgetary issue: you're weighing risks to the crew against the cost of refurbishment.