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

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, we have shown that 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 key cause of thymic atrophy during aging, and established that thymic atrophy can be mitigated by genetic or dietary complementation of catalase antioxidant activity. Here, we find that in addition to maintaining thymic mass with age, long-term increases in catalase activity may mitigate age-associated loss of stromal function. Our preliminary studies indicate that life-long overexpression of catalase in mitochondria of transgenic mice (mCAT Tg) results in increased TRA expression, mitigated acquisition of an aged global gene expression signature, and increased maintenance of cortico-medullary organization in aged mCAT Tg mice relative to non-transgenic littermates.