Figure 3.

Some proposed mechanisms of aging involving xanthine oxidoreductase (XOR) and its products. Uric acid (UA) and reactive oxygen species (ROS) can play a role in the downregulation of AMP-activated protein kinase/sirtuin-1 (AMPK/SIRT1) levels and in the upregulation of the mTOR and insulin/insulin-like growth factor (IGF) pathways. Nitric oxide (NO) produced by XOR nitrite reductase activity can inhibit cell proliferation, activating p21Waf1/Cip1 signaling and increasing the cyclin-dependent kinase 1 (CDK1) protein level. In addition, XOR-derived ROS can activate the ataxia telangiectasia mutated (ATM) enzyme, which upregulates p53, and causes IL1β release, as well as NLRP3 inflammasome activation and inflamm-aging. Pro-aging effects of XOR can be reduced by some pharmacological agents that inhibit the mTOR pathway (e.g., rapamycin) or interfere with XOR activity (e.g., resveratrol, metformin and spermine), as described in the text.