血清维生素A和B12水平与表观遗传加速衰老之间的非线性关联。

Non-linear association between serum levels of vitamins A and B12 and accelerated epigenetic aging.

作者信息

Ma Zhimin, An Mingxing, Gong Weiwei, Chen Xiangyu, Liang Mingbin, Zhang Jie, Du Xiaofu, Lu Feng, He Qingfang, Wang Meng, Zhong Jieming, Sun Ce

机构信息

Department of Chronic Disease Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.

Department of Epidemiology, School of Public Health, Southeast University, Nanjing, China.

出版信息

Front Nutr. 2025 Jul 28;12:1599205. doi: 10.3389/fnut.2025.1599205. eCollection 2025.

DOI:10.3389/fnut.2025.1599205

PMID:40791230

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12336032/

Abstract

BACKGROUND

Serum vitamins A and B12, as essential micronutrients, play pivotal roles in maintaining physiological homeostasis; however, the association between these vitamins and aging remains unclear. Therefore, this study aims to investigate potential threshold effects of these nutrients on accelerated biological aging using multidimensional DNA methylation biomarkers.

METHODS

This study included 2,530 participants with DNA methylation data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002. Two age acceleration metrics, derived from epigenetic clocks (PhenoAge and GrimAge), were calculated as the residuals obtained by regressing the epigenetic clock estimates on chronological age. Multivariable logistic regression models were used to analyze the association of vitamins A and B12 with epigenetic clocks. Additionally, generalized additive models and two-piecewise logistic regression were used to explore the non-linear relationships between vitamins A and B12 and epigenetic clocks.

RESULTS

Compared to the first quintile of vitamin A, the odds ratios (ORs) for PhenoAge acceleration in the next four quintiles were 1.24 (0.93-1.65), 1.04 (0.78-1.37), 0.95 (0.71-1.27), and 1.51 (1.13-2.01), respectively. No linear associations were found between vitamin B12 and PhenoAge acceleration, nor between vitamins A and B12 and GrimAge acceleration. However, the generalized additive model showed significant non-linear associations between serum levels of vitamins A and B12 and PhenoAge acceleration, with inflection points at 71.5 and 488.0 pg/mL, respectively. In addition, a non-linear association was observed between serum levels of vitamin A with GrimAge acceleration, with an inflection point at 71.8 μg/dL. Two-piecewise logistic regression also indicated that higher vitamin B12 delayed aging, while higher vitamin A accelerated aging. Sensitivity analyses showed a similar non-linear association between vitamins A and B12 and HannumAge acceleration.

CONCLUSION

This study suggests that higher vitamin A concentrations may be related to an increased risk of aging, while adequate vitamin B12 intake may offer protective benefits against epigenetic changes associated with aging.

摘要

背景

血清维生素A和维生素B12作为必需的微量营养素，在维持生理稳态中发挥着关键作用；然而，这些维生素与衰老之间的关联仍不明确。因此，本研究旨在使用多维DNA甲基化生物标志物来探究这些营养素对加速生物衰老的潜在阈值效应。

方法

本研究纳入了2530名参与者，他们拥有来自1999 - 2000年和2001 - 2002年国家健康与营养检查调查的DNA甲基化数据。从表观遗传时钟（PhenoAge和GrimAge）得出的两个年龄加速指标，被计算为通过将表观遗传时钟估计值对实足年龄进行回归得到的残差。多变量逻辑回归模型用于分析维生素A和维生素B12与表观遗传时钟的关联。此外，广义相加模型和两段式逻辑回归用于探究维生素A和维生素B12与表观遗传时钟之间的非线性关系。

结果

与维生素A的第一个五分位数相比，后四个五分位数中PhenoAge加速的比值比（OR）分别为1.24（0.93 - 1.65）、1.04（0.78 - 1.37）、0.95（0.71 - 1.27）和1.51（1.13 - 2.01）。未发现维生素B12与PhenoAge加速之间存在线性关联，维生素A和维生素B12与GrimAge加速之间也未发现线性关联。然而，广义相加模型显示血清维生素A和维生素B12水平与PhenoAge加速之间存在显著的非线性关联，拐点分别为71.5和488.0 pg/mL。此外，观察到血清维生素A水平与GrimAge加速之间存在非线性关联，拐点为71.8 μg/dL。两段式逻辑回归也表明较高的维生素B12延缓衰老，而较高的维生素A加速衰老。敏感性分析显示维生素A和维生素B12与HannumAge加速之间存在类似的非线性关联。