Comparative phenotyping of C57BL/6J substrains reveals distinctive patterns of cardiac aging

Abstract

Research in aging often refers to animal models, particularly C57BL/6J (B6J) mice, considered gold standard. However, B6J mice are distributed by different suppliers, which results in divers substrains exhibiting notable phenotypic differences. To ensure a suitable phenotype of cardiac aging, we performed heart analyses of young (5 months) and old B6J mice (24 months) from two substrains: B6JRj (Janvier) and B6JCrl mice (Charles River). In hearts of both substrains, myocardial fibrosis increased with age; however, only in old B6JRj mice cardiac hypertrophy associated with a decreased ejection fraction was observed. Gene set enrichment analysis in heart tissue using proteomic data revealed different age-associated pathway changes between the substrains, especially in oxidative phosphorylation. Functional assessment of isolated cardiomyocytes verified cardiac impairment during aging in B6JRj mice. Overall, results demonstrate that cardiac aging manifests as a moderate systolic dysfunction in B6JRj mice, while B6JCrl mice display no functional changes with age.