Increased antioxidant activity mitigates age-associated dysfunction of thymic stromal cells in aged mice.

Abstract

Abstract Age-associated thymic atrophy results in diminished production of new T lymphocytes and a concomitant decrease in responsiveness to new pathogens and vaccines. In addition to loss of thymic size with age, critical stromal functions, including tissue-restricted antigen (TRA) expression, are diminished with age. We previously identified deficiency of the hydrogen peroxide quenching enzyme catalase (CAT) in thymic stromal cells as a cause of thymic atrophy during aging, and established that thymic atrophy can be mitigated by genetic or dietary complementation of catalase antioxidant activity. Ongoing studies indicate that, in addition to increasing thymic cellularity, life-long overexpression of catalase in mitochondria of transgenic mice (mCAT Tg) results in increased TRA expression and decreased numbers of T cells binding self-peptide MHCII tetramers in aged mice. We also find mitigated acquisition of an aged global gene expression signature in aged mCAT Tg mice relative to non-transgenic littermates. Together, these results suggest that complementing catalase activity in thymic stromal cells mitigates age-associated declines in thymic function. Supported by N.I.H. R01AI121367 and N.I.H. R01AI121367-S