Enhanced expression of thioredoxin‐interacting‐protein regulates oxidative DNA damage and aging

The “free radical theory of aging” suggests that reactive oxygen species (ROS) are responsible for age‐related loss of cellular functions and, therefore, represent the main cause of aging. Redox regulation by thioredoxin‐1 (TRX) plays a crucial role in responses to oxidative stress. We show that thi...

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Bibliographic Details
Published in:	FEBS letters Vol. 592; no. 13; pp. 2297 - 2307
Main Authors:	Oberacker, Tina, Bajorat, Jörg, Ziola, Sabine, Schroeder, Anne, Röth, Daniel, Kastl, Lena, Edgar, Bruce A., Wagner, Wolfgang, Gülow, Karsten, Krammer, Peter H.
Format:	Journal Article
Language:	English
Published:	England John Wiley and Sons Inc 01-07-2018
Subjects:	Adult Aged aging Aging - genetics Aging - metabolism Animals Carrier Proteins - genetics Carrier Proteins - physiology Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology Cells, Cultured DNA damage DNA Damage - genetics Drosophila melanogaster HEK293 Cells Humans Jurkat Cells Longevity - genetics Middle Aged Oxidation-Reduction oxidative stress Oxidative Stress - genetics reactive oxygen species Reactive Oxygen Species - metabolism Research Letter Research Letters thioredoxin Thioredoxins - metabolism Up-Regulation - genetics Young Adult aging thioredoxin DNA damage oxidative stress reactive oxygen species
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Summary:	The “free radical theory of aging” suggests that reactive oxygen species (ROS) are responsible for age‐related loss of cellular functions and, therefore, represent the main cause of aging. Redox regulation by thioredoxin‐1 (TRX) plays a crucial role in responses to oxidative stress. We show that thioredoxin‐interacting protein (TXNIP), a negative regulator of TRX, plays a major role in maintaining the redox status and, thereby, influences aging processes. This role of TXNIP is conserved from flies to humans. Age‐dependent upregulation of TXNIP results in decreased stress resistance to oxidative challenge in primary human cells and in Drosophila. Experimental overexpression of TXNIP in flies shortens lifespan due to elevated oxidative DNA damage, whereas downregulation of TXNIP enhances oxidative stress resistance and extends lifespan.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by Barry Halliwell Tina Oberacker, Sabine Ziola and Jörg Bajorat contributed equally to this article. Karsten Gülow and Peter H. Krammer shared senior authorship.
ISSN:	0014-5793 1873-3468 1873-3468
DOI:	10.1002/1873-3468.13156