加速生物衰老与炎症性肠病风险：一项针对401,013名参与者的前瞻性研究。

Accelerated biological aging and risk of inflammatory bowel disease: A prospective study from 401,013 participants.

作者信息

Cao Baolong, Zhao Xiaoke, Lu Zhixi, Zhang Hongmei

机构信息

Department of Rehabilitation, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing 210008, China.

Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

出版信息

J Nutr Health Aging. 2025 Apr;29(4):100505. doi: 10.1016/j.jnha.2025.100505. Epub 2025 Feb 13.

DOI:10.1016/j.jnha.2025.100505

PMID:39952016

Abstract

OBJECTIVES

Relationship between biological aging and inflammatory bowel disease (IBD) remains unclear. We aimed to explore the associations of biological age and genetic predisposition with IBD and the predictive ability.

METHODS

Biological age and genetic predisposition were measured by PhenoAge and the polygenic risk score (PRS), respectively. The hazard ratio (HR) and 95% confidence interval (CI) of PhenoAge and combined PRS for Crohn's disease (CD) and ulcerative colitis (UC) were evaluated by Cox proportional hazards models. Additive interactions were examined to evaluate the joint effect. C statistic was employed to assess the predictive ability.

RESULTS

During the follow-up period of 5,320,311 person-years of 401,013 participants, 2467 patients with UC and 1262 patients with CD were observed. PhenoAge showed a significant association with an increased risk of incident IBD. Each standard deviation of PhenoAge acceleration correlated with a 38% (95% CI: 34%-41%), 35% (95% CI: 30%-38%), and 46% (95% CI: 41%-51%) increased risk of IBD, UC, and CD, respectively. Joint effects and additive interactions were noted between PhenoAge and the PRS. Individuals with a high PRS and the highest PhenoAge acceleration had the highest risk for UC (HR: 9.16, 95% CI: 7.08-11.85) and CD (7.72, 6.05-9.86), respectively. Incorporating PhenoAge and the PRS could enhance the accuracy of predicting IBD, with a highest C statistic of 0.71 for UC and 0.72 for CD.

CONCLUSION

Accelerated biological aging is associated with an increased risk of IBD, particularly in individuals with high genetic predisposition. Identifying individuals with accelerated biological aging has significant implications for reducing IBD risk.

摘要

目的

生物衰老与炎症性肠病（IBD）之间的关系仍不明确。我们旨在探讨生物年龄和遗传易感性与IBD的关联及其预测能力。

方法

分别通过PhenoAge和多基因风险评分（PRS）来测量生物年龄和遗传易感性。采用Cox比例风险模型评估PhenoAge和综合PRS对克罗恩病（CD）和溃疡性结肠炎（UC）的风险比（HR）及95%置信区间（CI）。通过检验相加交互作用来评估联合效应。采用C统计量评估预测能力。

结果

在401,013名参与者5320311人年的随访期内，观察到2467例UC患者和1262例CD患者。PhenoAge显示与IBD发病风险增加显著相关。PhenoAge加速每增加一个标准差，IBD、UC和CD的发病风险分别增加38%（95%CI：34%-41%）、35%（95%CI：30%-38%）和46%（95%CI：41%-51%）。观察到PhenoAge与PRS之间存在联合效应和相加交互作用。PRS高且PhenoAge加速最高的个体患UC（HR：9.16，95%CI：7.08-11.85）和CD（7.72，6.05-9.86）的风险最高。纳入PhenoAge和PRS可提高IBD预测的准确性，UC的最高C统计量为0.71，CD为0.72。