Adverse effects of low vitamin D level on mortality and morbidity are controversially discussed. Especially older people are at risk for vitamin D deficiency and therefore exposed to its potentially harmful consequences. A way of measuring differences in the biological age is through DNA methylation age (DNAm age) and its deviation from chronological age, DNAm age acceleration (DNAmAA). We previously reported on an association between vitamin D deficiency and higher 7-CpG DNAmAA in participants of the Berlin Aging Study II (BASE-II). In this study, we employ a quasi-interventional study design to assess the relationship between DNAmAA of five epigenetic clocks and vitamin D supplementation. Longitudinal data were available for 1,036 participants of BASE-II that were reexamined on average 7.4 years later in the GendAge study (mean age at follow-up: 75.6 years, SD = 3.8 years, age range: 64.9–94.1 years, 51.9% female). DNAmAA was estimated with the 7-CpG clock, Horvath’s clock, Hannum’s clock, PhenoAge, and GrimAge. Methylation data were obtained through methylation-sensitive single nucleotide primer extension (MS-SNuPE) or Illumina’s Infinium “MethylationEPIC” array. Vitamin D–deficient participants who chose to start vitamin D supplementation after baseline examination showed a 2.6-year lower 7-CpG DNAmAA (p = 0.011) and 1.3-year lower Horvath DNAmAA (p = 0.042) compared to untreated and vitamin D–deficient participants. DNAmAA did not statistically differ between participants with successfully treated vitamin D deficiency and healthy controls (p > 0.16). Therefore, we conclude that intake of vitamin D supplement is associated with lower DNAmAA in participants with vitamin D deficiency.

低维生素 D 水平对死亡率和发病率的不利影响存在争议。尤其是老年人有维生素 D 缺乏的风险，因此暴露于其潜在的有害后果。测量生物年龄差异的一种方法是通过DNA甲基化年龄（DNAm年龄）及其与实际年龄的偏差，DNAm年龄加速（DNAmAA）。我们之前报道了柏林老龄化研究 II (BASE-II) 参与者中维生素 D 缺乏与较高的 7-CpG DNAmAA 之间的关联。在这项研究中，我们采用准介入研究设计来评估五个表观遗传时钟的 DNAmAA 与维生素 D 补充剂之间的关系。1,036 名 BASE-II 参与者的纵向数据可用于平均 7.4 年后在 GendAge 研究中重新检查（平均随访年龄：75.6 岁，SD = 3.8 岁，年龄范围：64.9-94.1 岁，51.9% 为女性）。DNAmAA 是用 7-CpG 时钟、Horvath 时钟、Hannum 时钟、PhenoAge 和 GrimAge 估计的。甲基化数据通过甲基化敏感单核苷酸引物延伸 (MS-SNuPE) 或 Illumina 的 Infinium“MethylationEPIC”阵列获得。维生素 D 缺乏的参与者在基线检查后选择开始补充维生素 D，其 7-CpG DNAmAA 降低了 2.6 年。 与未经治疗和缺乏维生素 D 的参与者相比，p  = 0.011）和 1.3 年的 Horvath DNAmAA 降低（p = 0.042）。成功治疗维生素 D 缺乏症的参与者和健康对照者之间的 DNAmAA 没有统计学差异 ( p  > 0.16)。因此，我们得出结论，维生素 D 补充剂的摄入与维生素 D 缺乏症参与者的 DNAmAA 降低有关。