评估饮食质量、EpiNutrient 摄入量与表观遗传年龄之间的关系：一项观察性研究。

Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, Camerino, Italy.

Laboratory of Nutrition and Metabolic Epigenetics, Department of Health Sciences and Technology, ETH Zurich, Switzerland.

Am J Clin Nutr. 2024 Nov;120(5):1143-1155. doi: 10.1016/j.ajcnut.2024.08.033. Epub 2024 Oct 11.

BACKGROUND

DNA methylation (DNAm) has unique properties which makes it a potential biomarker for lifestyle-related exposures. Epigenetic clocks, particularly DNAm-based biological age predictors [epigenetic age (EA)], represent an exciting new area of clinical research and deviations of EA from chronological age [epigenetic age acceleration (EAA)] have been linked to overall health, age-related diseases, and environmental exposures.

OBJECTIVES

This observational study investigates the relationships between biological aging and various dietary factors within the LifeLines-DEEP Cohort. These factors include diet quality, processed food consumption, dietary glycemic load, and intake of vitamins involved in maintaining the epigenetic homeostasis (vitamins B-9, B-12, B-6, B-2, and C).

METHODS

Dietary records collected using food-frequency questionnaires were used to estimate diet quality [LifeLines Diet Score (LLDS)], measure the intake of unprocessed/ultraprocessed food according to the NOVA food classification system, and the adequacy of the dietary intake of vitamins B-9, B-12, B-2, B-6, and C. EA using Horvath, Hannum, Levine, and Horvath2 epigenetic clock models and DNAm-predicted telomere length (DNAm-TL) were calculated from DNAm data in 760 subjects. Associations between dietary factors and EAA were tested, adjusting for sex, energy intake, and body composition.

RESULTS

LLDS was associated with EAA (EAA_Horvath: β: -0.148; P = 1 × 10; EAA_Hannum: β: -0.148; P = 9 × 10; EAA_Levine: β: -0.174; P = 1 × 10; and EAA_Horvath2: β: -0.176; P = 4 × 10) and DNAm-TL (β: 0.116; P = 0.003). Particularly, EAA was associated with dietary glycemic load (EAA_Horvath: β: 0.476; P = 9 × 10; EAA_Hannum: β: 0.565; P = 1 × 10; EAA_Levine: β: 0.469; P = 5 × 10; EAA_Horvath2: β: 0.569; P = 1 × 10; and DNAmTL adjusted for age: β: -0.340; P = 2 × 10) and different measures of food processing (NOVA classes 1 and 4). Positive EAA was also associated with inadequate intake of vitamin B-12 (EAA_Horvath: β: -0.167; P = 0.002; EAA_Hannum: β: -0.144; P = 0.007; and EAA_Horvath2: β: -0.126; P = 0.019) and C (EAA_Hannum: β: -0.136; P = 0.010 and EAA_Horvath2: β: -0.151; P = 0.005).

CONCLUSIONS

Our findings corroborate the hypothesis that nutrition plays a pivotal role in influencing epigenetic homeostasis, especially DNAm, thereby contributing to individual health trajectories and the pace of aging.

背景

DNA 甲基化（DNAm）具有独特的性质，使其成为生活方式相关暴露的潜在生物标志物。表观遗传时钟，特别是基于 DNAm 的生物年龄预测因子[表观遗传年龄（EA）]，代表了临床研究的一个令人兴奋的新领域，EA 与实际年龄的偏差[表观遗传年龄加速（EAA）]与整体健康、与年龄相关的疾病和环境暴露有关。

目的

本观察性研究调查了 LifeLines-DEEP 队列中各种饮食因素与生物衰老之间的关系。这些因素包括饮食质量、加工食品消费、饮食血糖负荷以及参与维持表观遗传平衡的维生素摄入量（维生素 B-9、B-12、B-6、B-2 和 C）。

方法

使用食物频率问卷收集的饮食记录用于估计饮食质量[LifeLines 饮食评分（LLDS）]，根据 NOVA 食物分类系统测量未加工/超加工食品的摄入量，以及维生素 B-9、B-12、B-2、B-6 和 C 的饮食摄入量是否充足。使用 Horvath、Hannum、Levine 和 Horvath2 表观遗传时钟模型计算 760 名受试者的 EA，以及使用 DNAm 预测端粒长度（DNAm-TL）。调整性别、能量摄入和身体成分后，测试饮食因素与 EAA 的相关性。

结果

LLDS 与 EAA 相关（EAA_Horvath：β：-0.148；P=1×10；EAA_Hannum：β：-0.148；P=9×10；EAA_Levine：β：-0.174；P=1×10；EAA_Horvath2：β：-0.176；P=4×10）和 DNAm-TL（β：0.116；P=0.003）。特别是，EAA 与饮食血糖负荷有关（EAA_Horvath：β：0.476；P=9×10；EAA_Hannum：β：0.565；P=1×10；EAA_Levine：β：0.469；P=5×10；EAA_Horvath2：β：0.569；P=1×10；以及调整年龄后的 DNAmTL：β：-0.340；P=2×10）和不同的食物加工措施（NOVA 类别 1 和 4）。阳性 EAA 也与维生素 B-12 摄入不足有关（EAA_Horvath：β：-0.167；P=0.002；EAA_Hannum：β：-0.144；P=0.007；EAA_Horvath2：β：-0.126；P=0.019）和 C（EAA_Hannum：β：-0.136；P=0.010 和 EAA_Horvath2：β：-0.151；P=0.005）。