The application of base isolation to nuclear systems has been limited to date for some important reasons, including the deprivation of sufficient data for the long-term operation of such isolation devices and the lack of specific standards. Moreover, it is difficult to provide seismic protection in the vertical direction and to qualify the large-scale isolators up to experimentally large deformations in real dynamic conditions. The effect of aging on isolators is therefore one of the issues to be considered for the safety and reliability of base-isolated nuclear power plants (NPPs). Accounting for the variations of the post-aging parameters of the isolators on the structural performance of the plant, this study proposes a simplified and efficient method to update the analytical model of base-isolated structures based on mean-iterative neural networks (MINNs). A bilinear model with a zero length element was built to represent the characteristics of lead-rubber bearings for their numerical analysis. Analytical model updating by MINNs has been successfully performed, and the observed results are found to be in good agreement with those obtained from experiments. Additionally, it is observed that the stiffening or hardening with time in the shear properties of isolation devices affects the seismic performance of the base-isolated structure. Seismic design over the service life span of NPP structures should take these aging effects of the isolators into account.