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Enhanced expression of thioredoxin‐interacting‐protein regulates oxidative DNA damage and aging
Author(s) -
Oberacker Tina,
Bajorat Jörg,
Ziola Sabine,
Schroeder Anne,
Röth Daniel,
Kastl Lena,
Edgar Bruce A.,
Wagner Wolfgang,
Gülow Karsten,
Krammer Peter H.
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13156
Subject(s) - txnip , thioredoxin interacting protein , oxidative stress , downregulation and upregulation , thioredoxin , reactive oxygen species , microbiology and biotechnology , dna damage , oxidative phosphorylation , biology , biochemistry , dna , gene
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.