Sex-specific remodeling of proteasome complexes in lymph nodes of aged BTBR mice

Lymph node architecture and function are markedly altered with aging. We previously demonstrated that the lymph nodes of old C57BL/6 and BTBR male mice contain reduced levels of PA28αβ-capped proteasomes compared to young mice. Here, we examined aged BTBR females relative to aged males and found that proteasome remodeling occurs in a sex-specific manner. Specifically, old female exhibited higher immunoproteasome activity than old male, despite similar levels of proteasome and immunoproteasome subunit expression and proteasome complex assembly. In female mice activity was mostly driven by PA28αβ-capped 20S proteasomes that declined with age in males. These results highlight intriguing differences in proteasome assembly and activity between males and females providing evidence for sex-dependent changes in immunosenescence.