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ORIGINAL RESEARCH article

Front. Nutr.

Sec. Nutritional Epidemiology

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1599205

Nonlinear Association Between Serum Levels of Vitamin A and B12 and Accelerated Epigenetic Aging

Provisionally accepted
Zhimin MaZhimin Ma1Mingxing AnMingxing An2Weiwei GongWeiwei Gong1Xiangyu ChenXiangyu Chen1Mingbin LiangMingbin Liang1Jie ZhangJie Zhang1Xiaofu DuXiaofu Du1Feng LuFeng Lu1Qingfang HeQingfang He1Meng WangMeng Wang1Jieming ZhongJieming Zhong1Ce SunCe Sun3*
  • 1Zhejiang Center for Disease Control and Prevention (Zhejiang CDC), Hangzhou, Zhejiang Province, China
  • 2Southeast University, Nanjing, Jiangsu Province, China
  • 3Hangzhou Institute for Advanced Study, University of Chinese Academy of Science, Hangzhou, China

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Background: Serum vitamin A and B1212, as essential micronutrients, play pivotal roles in maintaining physiological homeostasis, but the associations between these vitamins and aging remains unclear. Therefore, this study aims to investigates potential threshold effects of these nutrients on accelerated biological aging using multi-dimensional DNA methylation biomarkers.Methods: This study included 2,530 participants with DNA methylation data from the National Health and Nutrition Examination Survey 1999Survey -2000Survey & 2001Survey -2002. Two age acceleration metrics of epigenetic clocks (PhenoAge, GrimAge) were calculated as the residuals from regressing epigenetic clocks on chronological age. Multivariable logistic regression models were used to analyze the associations of vitamin A and B12 with epigenetic clocks. Generalized additive model and twopiecewise logistic regression were used to explore the nonlinear associations.Results: Compared to the first quintile of vitamin A, the odds ratios (OR) for PhenoAge acceleration in the next four quintiles were 1.

Keywords: accelerated epigenetic aging, biological aging, Vitamin A, Vitamin B12, nonlinear association

Received: 24 Mar 2025; Accepted: 07 Jul 2025.

Copyright: © 2025 Ma, An, Gong, Chen, Liang, Zhang, Du, Lu, He, Wang, Zhong and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ce Sun, Hangzhou Institute for Advanced Study, University of Chinese Academy of Science, Hangzhou, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material