本报北京电(耿令令)运动作为生命活动的生物学基础，是公认高效且低成本的健康促进与抗衰干预策 略。然而，其深层分子机制尚未完全阐明。6月25日，首都医科大学宣武医院王思研究员团队联合中国 科学院动物研究所刘光慧研究员、曲静研究员、宋默识研究员及国家生物信息中心张维绮研究员团队， 在Cell杂志上就此发表了研究论文。 研究团队历时6年，首次系统解析了人体对急性单次运动与长期规律运动的分子细胞动态响应谱，揭示 肾脏是运动效应的关键应答器官——其内源代谢物甜菜碱作为衰老延缓的核心分子信使，通过靶向抑制 天然免疫枢纽激酶TBK1，协同阻遏炎症并缓解多器官衰老进程。该发现不仅为"运动即青春之泉"的古 老认知提供分子注脚，更开创了基于"运动模拟药物"实现系统性抗衰干预的全新策略。 化学生物学研究揭示，天然免疫激酶TBK1是甜菜碱的直接作用靶点。甜菜碱特异性结合TBK1并抑制其 激酶活性，进而阻断下游IRF3/NF-κB信号通路激活，抑制促炎因子表达。在感染性炎症及自然衰老的 模型中，口服甜菜碱显著降低多组织TBK1磷酸化水平，有效减少免疫细胞浸润并抑制促炎因子释放。 该研究构建了多模态时空动态分析框架，系统地揭示了"运动悖 ...

Core Viewpoint - The article discusses the molecular mechanisms underlying the health benefits of exercise and introduces betaine as a potential exercise mimetic for geroprotection, providing a new strategy for anti-aging interventions [1][3][22]. Group 1: Research Findings - The research team conducted a six-year study that systematically analyzed the molecular and cellular responses of the human body to acute and long-term exercise, identifying the kidneys as a key organ responding to exercise effects [2][11]. - Betaine was found to be a core molecular messenger for delaying aging, targeting and inhibiting the natural immune hub kinase TBK1, which helps to alleviate inflammation and slow down the aging process in multiple organs [2][15]. - The study established a multi-modal data coupling analysis framework, breaking down the complex biological responses to exercise into a quantifiable dynamic network [9][20]. Group 2: Mechanisms of Exercise-Induced Anti-Aging - The research revealed distinct effects of acute versus long-term exercise, with acute exercise triggering a "survival stress-type" metabolic storm, while long-term exercise promotes a health-oriented metabolic-immune homeostasis [11][12]. - Long-term exercise was shown to rejuvenate T lymphocytes by enhancing genomic and epigenetic stability, activating NRF2 pathways to suppress inflammatory factors, and promoting T cell survival and proliferation [12][14]. - The study demonstrated that long-term exercise significantly increases kidney betaine levels, with choline dehydrogenase (CHDH) identified as a key regulatory enzyme in this process [13][14]. Group 3: Implications of Betaine as an Exercise Mimetic - Betaine was shown to effectively simulate the benefits of long-term exercise, improving various aging-related cellular phenotypes in human diploid cells and extending healthy lifespan in aged mice [14][22]. - The study confirmed that betaine specifically binds to and inhibits TBK1 kinase activity, blocking downstream inflammatory signaling pathways, thus reducing immune cell infiltration and inflammatory factor release [15][20]. - The findings suggest that betaine could serve as a potential anti-aging alternative for elderly populations who cannot tolerate high-intensity exercise, marking a new paradigm in the development of exercise-mimicking drugs [20][22].