Circuit reliability is affected by various fabrication-time and run-time effects. Fabrication-induced process variation has significant impact on circuit performance and reliability. Various aging effects, such as negative bias temperature instability, cause continuous performance and reliability degradation during circuit run-time usage. In this work, we present a statistical analysis framework that characterizes the lifetime reliability of nanometer-scale integrated circuits by jointly considering the impact of fabrication-induced process variation and run-time aging effects. More specifically, our work focuses on characterizing circuit threshold voltage lifetime variation and its impact on circuit timing due to process variation and the negative bias temperature instability effect, a primary aging effect in nanometer-scale integrated circuits. The proposed work is capable of characterizing the overall circuit lifetime reliability, as well as efficiently quantifying the vulnerabilities of individual circuit elements. This analysis framework has been carefully validated and integrated into an iterative design flow for circuit lifetime reliability analysis and optimization.