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

Tina Oberacker | Jörg Bajorat | Sabine Ziola | Anne Schroeder | Daniel Röth | Lena Kastl | Bruce A Edgar | Wolfgang Wagner | Karsten Gülow | Peter H Krammer
FEBS letters | 2018

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.

Pubmed ID: 29897613

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010949

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QIAGEN (tool)

RRID:SCR_008539

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RRID:SCR_013527

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RRID:SCR_002845

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RRID:DGGR_115633

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RRID:MGI:2683685

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RRID:CVCL_0065

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RRID:SCR_006457

Collects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.

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