Zhao Cong, Zhao Leying, Liu Yang, Sun Li-Qiao, Li Xin-Rong, Wang Yaoxian, Sun Weiwei
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Department of Chinese Medicine, Cangzhou Central Hospital, Cangzhou, China.
Front Nutr. 2025 Apr 22;12:1569798. doi: 10.3389/fnut.2025.1569798. eCollection 2025.
Serum uric acid (SUA), a byproduct of purine metabolism, exerts both antioxidant and pro-inflammatory effects, making its role in aging and chronic diseases a subject of ongoing debate. Despite this, the mechanisms by which SUA influences the aging process remain poorly understood.
We analyzed data from the NHANES (1999-2010) and CHARLS (2011-2015) cohorts to investigate SUA's impact on biological aging. Generalized linear regression models assessed SUA's effect on biological aging markers [ΔKDM-BA, ΔPhenoAge, and allostatic load (AL)], while Cox regression models estimated its association with all-cause and premature mortality. Dose-response relationships between SUA levels and aging markers (ΔKDM-BA, ΔPhenoAge, and AL), as well as all-cause and premature mortality, were evaluated using restricted cubic splines (RCS).
In both cohorts, elevated SUA levels were significantly associated with accelerated aging. In the NHANES cohort, for each 1 mg/dL increase in SUA, ΔKDM-BA increased by 0.52 years (95% CI: 0.43-0.61, < 0.0001), and AL increased by 0.38 (95% CI: 0.29-0.47, < 0.0001). In the CHARLS cohort, SUA was similarly linked to an increase in ΔKDM-BA by 0.65 years (95% CI: 0.57-0.74, < 0.0001) and AL by 0.15 (95% CI: 0.12-0.18, < 0.0001). RCS analysis revealed a nonlinear association between SUA and ΔKDM-BA in NHANES, with a more pronounced acceleration of aging when SUA levels exceeded 4.16 mg/dL (nonlinear < 0.0001). In CHARLS, SUA showed a nonlinear relationship with ΔKDM-BA (nonlinear = 0.01). Additionally, in NHANES, SUA levels were associated with increased all-cause (HR: 1.04, 95% CI: 1.01-1.07, = 0.01) and premature mortality (HR: 1.06, 95% CI: 1.00-1.13, = 0.046). RCS analysis further demonstrated a U-shaped nonlinear relationship between SUA levels and both all-cause and premature mortality. In contrast, SUA did not show a significant association with mortality outcomes in the CHARLS cohort.
Elevated SUA is associated with accelerated biological aging in both U.S. and Chinese populations, but its link to mortality was evident only in the NHANES cohort. These findings highlight SUA as a potential aging marker and call for further population-specific investigation.
血清尿酸（SUA）是嘌呤代谢的副产物，具有抗氧化和促炎作用，这使得其在衰老和慢性疾病中的作用一直存在争议。尽管如此，SUA影响衰老过程的机制仍知之甚少。
我们分析了美国国家健康与营养检查调查（NHANES，1999 - 2010年）和中国健康与养老追踪调查（CHARLS，2011 - 2015年）队列的数据，以研究SUA对生物衰老的影响。广义线性回归模型评估了SUA对生物衰老标志物[ΔKDM - BA、ΔPhenoAge和应激负荷（AL）]的影响，而Cox回归模型估计了其与全因死亡率和过早死亡率的关联。使用受限立方样条（RCS）评估SUA水平与衰老标志物（ΔKDM - BA、ΔPhenoAge和AL）以及全因死亡率和过早死亡率之间的剂量反应关系。
在两个队列中，SUA水平升高均与加速衰老显著相关。在NHANES队列中，SUA每升高1mg/dL，ΔKDM - BA增加0.52岁（95%置信区间：0.43 - 0.61，P < 0.0001），AL增加0.38（95%置信区间：0.29 - 0.47，P < 0.0001）。在CHARLS队列中，SUA同样与ΔKDM - BA增加0.65岁（95%置信区间：0.57 - 0.74，P < 0.0001）和AL增加0.15（95%置信区间：0.12 - 0.18，P < 0.0001）相关。RCS分析显示，在NHANES队列中，SUA与ΔKDM - BA之间存在非线性关联，当SUA水平超过4.16mg/dL时，衰老加速更为明显（非线性P < 0.0001）。在CHARLS队列中，SUA与ΔKDM - BA呈非线性关系（非线性P = 0.01）。此外，在NHANES队列中，SUA水平与全因死亡率增加（风险比：1.04，95%置信区间：1.01 - 1.07，P = 0.01）和过早死亡率增加（风险比：一1.06，95%置信区间：1.00 - 1.13，P = 0.046）相关。RCS分析进一步证明了SUA水平与全因死亡率和过早死亡率之间呈U形非线性关系。相比之下，在CHARLS队列中，SUA与死亡结局无显著关联。
SUA升高与美国和中国人群的生物衰老加速相关，但仅在NHANES队列中其与死亡率的关联明显。这些发现突出了SUA作为一种潜在衰老标志物的作用，并呼吁进行进一步的针对特定人群的研究。
