In this study, we compared N-methyl-D-aspartate receptor type 1 (NMDAR1) and 4-hydroxynonenal (4-HNE) in the hippocampus of D-galactose (D-gal)-induced and naturally aging models of mice. These markers represent general phenotypes in aging, and they allowed us to examine the possibility of D-gal as a chemical model agent for aging. We observed an age-dependent reduction of NMDAR1 and an increase in 4-HNE in the dentate gyrus, CA1, and CA3 regions of the hippocampus via immunohistochemistry and western blot analyses. In the D-gal-induced chemical aging model, we observed similar changes in NMDAR1 and 4-HNE although the degree of reduction/increase in NMDAR1/4-HNE was not as severe as that in the naturally aged mice. These results suggest that the D-gal-induced aging model is comparable to naturally aged mice and may be useful for studies of the aging hippocampus.