Tumor Immunology Program (D030), German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Research Center (DKFZ), Center for Molecular Biology, University of Heidelberg Alliance, Germany.
FEBS Lett. 2018 Jul;592(13):2297-2307. doi: 10.1002/1873-3468.13156. Epub 2018 Jun 27.
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.
“衰老自由基理论”表明，活性氧（ROS）是导致与年龄相关的细胞功能丧失的原因，因此是衰老的主要原因。硫氧还蛋白-1（TRX）的氧化还原调节在应对氧化应激中起着至关重要的作用。我们表明，硫氧还蛋白相互作用蛋白（TXNIP），TRX 的负调节剂，在维持氧化还原状态方面起着重要作用，从而影响衰老过程。这种 TXNIP 的作用从苍蝇到人类都是保守的。TXNIP 的年龄依赖性上调导致原代人细胞和果蝇对氧化应激挑战的抵抗力降低。在果蝇中过表达 TXNIP 会由于氧化 DNA 损伤而导致寿命缩短，而下调 TXNIP 会增强氧化应激抗性并延长寿命。
