DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age, epigenetic clocks, for many species. Using a custom methylation array, we generated DNA methylation data from n = 238 porcine tissues including blood, bladder, frontal cortex, kidney, liver, and lung, from domestic pigs (Sus scrofa domesticus) and minipigs (Wisconsin Miniature Swine™). Samples used in this study originated from Large White X Landrace crossbred pigs, Large White X Minnesota minipig crossbred pigs, and Wisconsin Miniature Swine™. We present 4 epigenetic clocks for pigs that are distinguished by their compatibility with tissue type (pan-tissue and blood clock) and species (pig and human). Two dual-species human-pig pan-tissue clocks accurately measure chronological age and relative age, respectively. We also characterized CpGs that differ between minipigs and domestic pigs. Strikingly, several genes implicated by our epigenetic studies of minipig status overlap with genes (ADCY3, TFAP2B, SKOR1, and GPR61) implicated by genetic studies of body mass index in humans. In addition, CpGs with different levels of methylation between the two pig breeds were identified proximal to genes involved in blood LDL levels and cholesterol synthesis, of particular interest given the minipig’s increased susceptibility to cardiovascular disease compared to domestic pigs. Thus, breed-specific differences of domestic and minipigs may potentially help to identify biological mechanisms underlying weight gain and aging-associated diseases. Our porcine clocks are expected to be useful for elucidating the role of epigenetics in aging and obesity, and the testing of anti-aging interventions.

DNA 甲基化谱已成功用于开发许多物种的高度准确的年龄生物标志物、表观遗传时钟。使用定制的甲基化阵列，我们从n  = 238 个猪组织中生成 DNA 甲基化数据，包括来自家猪 ( Sus scrofa domesticus) 和小型猪 (Wisconsin Miniature Swine™)。本研究中使用的样本来自大白 X 长白杂交猪、大白 X 明尼苏达小型杂交猪和威斯康星小型猪™。我们为猪提供了 4 个表观遗传时钟，这些时钟通过与组织类型（泛组织和血时钟）和物种（猪和人类）的相容性来区分。两个双物种人猪泛组织时钟分别准确测量实足年龄和相对年龄。我们还表征了小型猪和家猪之间不同的 CpG。引人注目的是，我们对小型猪状态的表观遗传学研究涉及的几个基因与人类体重指数遗传研究涉及的基因（ADCY3、TFAP2B、SKOR1 和 GPR61）重叠。此外，两种猪品种之间甲基化水平不同的 CpG 被鉴定为与参与血液 LDL 水平和胆固醇合成的基因接近，考虑到与家猪相比，小型猪对心血管疾病的易感性增加，这一点特别令人感兴趣。因此，家猪和小型猪的品种特异性差异可能有助于确定体重增加和衰老相关疾病的生物学机制。我们的猪时钟有望用于阐明表观遗传学在衰老和肥胖中的作用，以及测试抗衰老干预措施。家猪和小型猪的品种特异性差异可能有助于确定体重增加和衰老相关疾病的生物学机制。我们的猪时钟有望用于阐明表观遗传学在衰老和肥胖中的作用，以及测试抗衰老干预措施。家猪和小型猪的品种特异性差异可能有助于确定体重增加和衰老相关疾病的生物学机制。我们的猪时钟有望用于阐明表观遗传学在衰老和肥胖中的作用，以及测试抗衰老干预措施。