IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy.
DIMES-Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, Bologna, Italy.
J Gerontol A Biol Sci Med Sci. 2019 Jan 1;74(1):1-8. doi: 10.1093/gerona/gly048.
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8,823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria, we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally, we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt-signaling pathways in the aging of human liver.
来自老年健康供体的肝移植的可行性表明，该器官在衰老过程中能够保持其功能。为了探索这一现象的生物学基础，我们使用 Infinium HumanMethylation450 BeadChip 对取自 45 名年龄在 13 至 90 岁之间的健康肝脏供体的肝脏活检样本进行了特征描述，以确定其表观遗传特征。分析表明，DNA 甲基化模式发生了大规模重塑，有 8823 个与年龄相关的差异甲基化 CpG 探针。值得注意的是，这些与年龄相关的变化在 60 岁以后趋于平稳，这与 Horvath 的生物钟一致。使用严格的选择标准，我们进一步确定了包括 75 个基因组区域的老化肝脏的 DNA 甲基化特征。我们证明，与其他组织相比，该特征在肝脏中是特异性的，并且能够检测与肥胖相关的生物年龄加速效应。最后，我们将 DNA 甲基化测量与可用的表达数据相结合。尽管两种组学特征的交集较低，但两种方法都表明上皮-间充质转化和 Wnt 信号通路在人类肝脏衰老中起着以前未被认识的作用。
