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Cell Rep. 2015 Aug 18;12(7):1071-9. doi: 10.1016/j.celrep.2015.07.008. Epub 2015 Aug 6.

Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.

Author information

1
Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
2
Departments of Biological Structure and Immunology, The University of Washington, South Lake Union E-411, 750 Republican Street, Box 358059, Seattle, WA 98109, USA.
3
Free Radical Biology and Aging Research Program, The Oklahoma Medical Research Foundation, MS 21, 825 NE 13(th) Street, Oklahoma City, OK 73104, USA.
4
Department of Pathology, The University of Washington, 1959 NE Pacific Avenue, HSB K-081, Box 357705, Seattle, WA 98195, USA.
5
Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address: htpetrie@scripps.edu.

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.

PMID:
26257169
PMCID:
PMC4797338
DOI:
10.1016/j.celrep.2015.07.008
[Indexed for MEDLINE]
Free PMC Article

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