Mechanobiology Institute, National University of Singapore, Singapore, Singapore.
FIRC Institute for Molecular Oncology (IFOM), Milan, Italy.
Sci Rep. 2020 Nov 5;10(1):19086. doi: 10.1038/s41598-020-76117-y.
For systematic identification of transcription signatures of human cell aging, we carried out Weighted Gene Co-expression Network Analysis (WGCNA) with the RNA-sequencing data generated with young to old human dermal fibroblasts. By relating the modules to the donor's traits, we uncovered the natural aging- and premature aging disease-associated modules. The STRING functional association networks built with the core module memberships provided a systematic overview of genome-wide transcriptional changes upon aging. We validated the selected candidates via quantitative reverse transcription PCR (RT-qPCR) assay with young and aged human fibroblasts, and uncovered several genes involved in ECM, cell, and nuclear mechanics as a potential aging biomarker. Collectively, our study not only provides a snapshot of functional changes during human fibroblast aging but also presents potential aging markers that are relevant to cell mechanics.
为了系统地鉴定人类细胞衰老的转录特征,我们对来自年轻至年老的人类真皮成纤维细胞的 RNA 测序数据进行了加权基因共表达网络分析(WGCNA)。通过将模块与供体的特征相关联,我们揭示了自然衰老和与早衰疾病相关的模块。利用核心模块成员关系构建的 STRING 功能关联网络提供了衰老过程中全基因组转录变化的系统概述。我们通过对年轻和年老的人类成纤维细胞进行定量逆转录聚合酶链反应(RT-qPCR)检测,对选定的候选基因进行了验证,并发现了几个涉及细胞外基质、细胞和核力学的基因,它们可能是潜在的衰老生物标志物。总的来说,我们的研究不仅提供了人类成纤维细胞衰老过程中功能变化的快照,还提出了与细胞力学相关的潜在衰老标志物。