Table1_Tanshinone IIA delays liver aging by modulating oxidative stress.XLSX

Organ-specific aging is increasingly recognized for its research significance, with liver aging demonstrating particular relevance due to its central role in metabolism. We have pioneered the discovery that the expression of ESRRG in the liver positively correlates with age and have established its association with clinical characteristics, including hepatic edema. Our findings link liver aging to a shift in oxidative stress states, where ESRRG, a crucial nuclear receptor responsive to oxidative stress, may be modulated by various small molecules. Through virtual screening of a natural medicinal molecule database followed by further validation, we confirmed that the natural compound Tanshinone IIA mitigates oxidative stress-induced damage in the liver via the ESRRG/Cyp2e1 pathway, thus decelerating liver aging. Importantly, our study also explores the dynamic impact of Tanshinone IIA on ESRRG conformation, providing a profound understanding of its molecular interactions with ESRRG and laying a foundation for the rational design of small molecules based on natural compounds.

器官特异性衰老（Organ-specific aging）的研究价值日益受到学界重视，而肝脏作为机体代谢中枢，其衰老相关研究尤为关键。本研究率先发现肝脏中ESRRG的表达水平与年龄呈正相关，并证实其与包括肝水肿在内的多项临床特征存在关联。研究结果表明，肝脏衰老与氧化应激状态的动态改变密切相关；作为响应氧化应激的关键核受体，ESRRG可被多种小分子物质调控。本研究通过对天然药物分子数据库开展虚拟筛选，并经后续实验验证，证实天然化合物丹参酮IIA（Tanshinone IIA）可通过ESRRG/Cyp2e1通路减轻氧化应激诱导的肝脏损伤，进而延缓肝脏衰老。尤为重要的是，本研究还揭示了丹参酮IIA对ESRRG构象的动态调控效应，深化了二者分子互作机制的认知，为基于天然化合物的小分子合理设计奠定了坚实的理论基础。