title: Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.
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.
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Ann V
authors.initials: AV
authors.lastname: Griffith
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Venables
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Departments of Biological Structure and Immunology, The University of Washington, South Lake Union E-411, 750 Republican Street, Box 358059, Seattle, WA 98109, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Farr
authors.affiliation: Free Radical Biology and Aging Research Program, The Oklahoma Medical Research Foundation, MS 21, 825 NE 13(th) Street, Oklahoma City, OK 73104, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: van Remmen
authors.affiliation: Free Radical Biology and Aging Research Program, The Oklahoma Medical Research Foundation, MS 21, 825 NE 13(th) Street, Oklahoma City, OK 73104, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Szweda
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fallahi
authors.affiliation: Department of Pathology, The University of Washington, 1959 NE Pacific Avenue, HSB K-081, Box 357705, Seattle, WA 98195, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Rabinovitch
authors.affiliation: Department of Immunology and Microbial Sciences, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address: htpetrie@scripps.edu.
authors.forename: Howard T
authors.initials: HT
authors.lastname: Petrie
mesh_terms: D019588:Aging, Premature / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology*
chemical_list: D006861:Hydrogen Peroxide; D002374:Catalase