Sun Mengzhen, Zhang Shixuan, Zhang Hui, Zhang Na, Wu Weicheng, Cao Yuanfei, Wang Mengjing, Chen Jing, Jiang Xiaoyan, Sun Xuehui, Wang Xiaofeng, Zhang Qi
Human Phenome Institute and MOE Key Laboratory of Contemporary Anthropology, School of Life Science, Fudan University, Shanghai, China.
Fudan University People's Hospital of Rugao Joint Research Institute of Longevity and Aging, Rugao, Jiangsu Province, China.
Aging Clin Exp Res. 2025 Oct 11;37(1):294. doi: 10.1007/s40520-025-03198-y.
Physical dysfunction is a preclinical stage of disability in older adults, linked to severe adverse outcomes such as death and hospitalization. Maximal tubular reabsorption of phosphate (TmP/GFR), as a key biomarker of phosphate metabolism, may be related to physical dysfunction, but this relationship has not yet been explored.
Using data from the Rugao Longitudinal Ageing Study (RLAS), longitudinal logistic regression was employed to explore the relationship between abnormal TmP/GFR and physical dysfunction. For validation, the UK Biobank dataset was combined, and mendelian randomization (MR) was conducted to investigate causality. The maximal phosphate reabsorption was assessed using TmP/GFR, while physical dysfunction were evaluated through grip strength and the Timed Up and Go (TUG) test.
During the four-year follow-up, 89 (13.55%) and 279 (40.85%) participants were identified as having a new onset of decreased grip and TUG. The abnormal TmP/GFR population had a significantly higher risk of decreased grip (OR 2.03, 95% CI 1.20-3.49) and decreased TUG (OR 1.49, 95% CI 1.05-2.12). MR analysis demonstrated the causal effect of TmP/GFR dysfunction population had significantly lower grip and lower walking speed.
This study first identifies abnormal TmP/GFR as a novel biomarker of physical dysfunction in older adults. Additionally, its causal relationship further substantiates the reliability of this finding. Abnormal TmP/GFR enables early detection of physical dysfunction, facilitating the prevention of severe adverse outcomes.
身体功能障碍是老年人残疾的临床前期阶段,与死亡和住院等严重不良后果相关。作为磷酸盐代谢的关键生物标志物,最大肾小管磷酸盐重吸收(TmP/GFR)可能与身体功能障碍有关,但这种关系尚未得到探索。
利用如皋纵向老龄化研究(RLAS)的数据,采用纵向逻辑回归探讨异常TmP/GFR与身体功能障碍之间的关系。为进行验证,合并了英国生物银行数据集,并进行孟德尔随机化(MR)以研究因果关系。使用TmP/GFR评估最大磷酸盐重吸收,而通过握力和计时起立行走(TUG)测试评估身体功能障碍。
在四年的随访期间,89名(13.55%)和279名(40.85%)参与者被确定出现了新的握力下降和TUG情况。异常TmP/GFR人群出现握力下降(OR 2.03,95%CI 1.20 - 3.49)和TUG下降(OR 1.49,95%CI 1.05 - 2.12)的风险显著更高。MR分析表明,TmP/GFR功能障碍人群的因果效应表现为握力显著降低和步行速度减慢。
本研究首次确定异常TmP/GFR是老年人身体功能障碍的一种新型生物标志物。此外,其因果关系进一步证实了这一发现的可靠性。异常TmP/GFR能够早期检测身体功能障碍,有助于预防严重不良后果。