Drouard Gabin, Suhonen Sannimari, Heikkinen Aino, Wang Zhiyang, Kaprio Jaakko, Ollikainen Miina
Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Aging Cell. 2025 May 5:e70088. doi: 10.1111/acel.70088.
Connections between the multi-ome and epigenetic age acceleration (EAA), and especially whether these are influenced by genetic or environmental factors, remain underexplored. We therefore quantified associations between the multi-ome comprising four layers-the proteome, metabolome, external exposome (here, sociodemographic factors), and specific exposome (here, lifestyle)-with six different EAA estimates. Two twin cohorts were used in a discovery-replication scheme, comprising, respectively, young (N = 642; mean age = 22.3) and older (N = 354; mean age = 62.3) twins. Within-pair twin designs were used to assess genetic and environmental effects on associations. We identified 40 multi-omic factors, of which 28 were proteins, associated with EAA in the young twins while adjusting for sex, smoking, and body mass index. Within-pair analyses revealed that genetic confounding influenced these associations heterogeneously, with six multi-omic factors -matrix metalloproteinase 9, complement component C6, histidine, glycoprotein acetyls, lactate, and neighborhood percentage of nonagenarians- remaining significantly associated with EAA, independent of genetic effects. Replication analyses showed that some associations assessed in young twins were consistent in older twins. Our study highlights the differential influence of genetic effects on the associations between the multi-ome and EAA and shows that some, but not all, of the associations persist into adulthood.
多组学与表观遗传年龄加速（EAA）之间的联系，尤其是这些联系是否受遗传或环境因素影响，仍未得到充分探索。因此，我们量化了由蛋白质组、代谢组、外部暴露组（此处为社会人口统计学因素）和特定暴露组（此处为生活方式）四层组成的多组学与六种不同的EAA估计值之间的关联。在一项发现-重复研究方案中使用了两个双胞胎队列，分别包括年轻双胞胎（N = 642；平均年龄 = 22.3岁）和年长双胞胎（N = 354；平均年龄 = 62.3岁）。采用配对双胞胎设计来评估遗传和环境因素对关联的影响。在对性别、吸烟和体重指数进行校正后，我们在年轻双胞胎中确定了40个与EAA相关的多组学因素，其中28个是蛋白质。配对分析表明，遗传混杂对这些关联的影响存在异质性，六种多组学因素——基质金属蛋白酶9、补体成分C6、组氨酸、糖蛋白乙酰化物、乳酸和百岁老人在邻里中的比例——与EAA仍显著相关，不受遗传效应影响。重复分析表明，在年轻双胞胎中评估的一些关联在年长双胞胎中是一致的。我们的研究强调了遗传效应在多组学与EAA之间关联中的差异影响，并表明部分（而非全部）关联会持续到成年期。
