Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency

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...

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Main Authors:	Griffith, Ann V, Venables, Thomas, Shi, Jianjun, Farr, Andrew, van Remmen, Holly, Szweda, Luke, Fallahi, Mohammad, Rabinovitch, Peter, Petrie, Howard T.
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797338/

id	pubmed-4797338
recordtype	oai_dc
spelling	pubmed-47973382016-08-18 Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency Griffith, Ann V Venables, Thomas Shi, Jianjun Farr, Andrew van Remmen, Holly Szweda, Luke Fallahi, Mohammad Rabinovitch, Peter Petrie, Howard T. Article 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. 2015-08-06 2015-08-18 /pmc/articles/PMC4797338/ /pubmed/26257169 http://dx.doi.org/10.1016/j.celrep.2015.07.008 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Griffith, Ann V Venables, Thomas Shi, Jianjun Farr, Andrew van Remmen, Holly Szweda, Luke Fallahi, Mohammad Rabinovitch, Peter Petrie, Howard T.
spellingShingle	Griffith, Ann V Venables, Thomas Shi, Jianjun Farr, Andrew van Remmen, Holly Szweda, Luke Fallahi, Mohammad Rabinovitch, Peter Petrie, Howard T. Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency
author_facet	Griffith, Ann V Venables, Thomas Shi, Jianjun Farr, Andrew van Remmen, Holly Szweda, Luke Fallahi, Mohammad Rabinovitch, Peter Petrie, Howard T.
author_sort	Griffith, Ann V
title	Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency
title_short	Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency
title_full	Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency
title_fullStr	Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency
title_full_unstemmed	Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency
title_sort	metabolic damage and premature thymus aging caused by stromal catalase deficiency
description	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.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797338/
_version_	1613553877479587840

Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency

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