Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency

Ann V Griffith, Thomas Venables, Jianjun Shi, Andrew Farr, Holly van Remmen, Luke Szweda, Mohammad Fallahi, Peter Rabinovitch, Howard T. Petrie

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment.

Original languageEnglish (US)
Pages (from-to)1071-1079
Number of pages9
JournalCell Reports
Volume12
Issue number7
DOIs
StatePublished - Aug 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Griffith, A. V., Venables, T., Shi, J., Farr, A., van Remmen, H., Szweda, L., Fallahi, M., Rabinovitch, P., & Petrie, H. T. (2015). Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency. Cell Reports, 12(7), 1071-1079. https://doi.org/10.1016/j.celrep.2015.07.008