Transcriptome analysis of human ageing in male skin shows mid-life period of variability and central role of NF-κB.
Transcriptome analysis of human ageing in male skin shows mid-life period of variability and central role of NF-κB.
复制标题
人类男性皮肤老化的转录组分析表明，中年时期的变化和 NF-κB 的核心作用。
DOI：
10.1038/srep26846
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发表时间：
2016-05-27
影响因子：
4.6
通讯作者：
Fear MW
中科院分区：
文献类型：
--
作者：
Haustead DJ;Stevenson A;Saxena V;Marriage F;Firth M;Silla R;Martin L;Adcroft KF;Rea S;Day PJ;Melton P;Wood FM;Fear MW
年龄是疾病病理和治疗反应的一个重要因素，这是众所周知的，但人类随年龄增长而发生的分子变化仍不明确。在此，通过对健康男性人类皮肤进行转录组分析，我们证明存在一个主要在中年发生的、转录组范围内表达变化显著升高的时期。在此时期之前和之后，转录组似乎随着年龄增长发生更小的线性变化。对中年短暂变化的功能分析表明，这是一个与NF -κB和TNF信号通路相关的代谢活动增强和细胞损伤的时期。通过荟萃分析，我们还表明存在随年龄增长的全局的、不依赖组织的线性转录组变化，这些变化似乎受NF -κB调控。这些结果表明，人类皮肤的衰老与一个关键的中年时期相关，在此期间转录组发生广泛变化，在此之前和之后转录组以相对稳定的线性变化速率变化。这些数据为了解与正常衰老相关的分子变化提供了见解，并将有助于更好地理解与衰老相关的日益重要的病理变化。
Age is well-known to be a significant factor in both disease pathology and response to treatment, yet the molecular changes that occur with age in humans remain ill-defined. Here, using transcriptome profiling of healthy human male skin, we demonstrate that there is a period of significantly elevated, transcriptome-wide expression changes occurring predominantly in middle age. Both pre and post this period, the transcriptome appears to undergo much smaller, linear changes with increasing age. Functional analysis of the transient changes in middle age suggest a period of heightened metabolic activity and cellular damage associated with NF-kappa-B and TNF signaling pathways. Through meta-analysis we also show the presence of global, tissue independent linear transcriptome changes with age which appear to be regulated by NF-kappa-B. These results suggest that aging in human skin is associated with a critical mid-life period with widespread transcriptome changes, both preceded and proceeded by a relatively steady rate of linear change in the transcriptome. The data provides insight into molecular changes associated with normal aging and will help to better understand the increasingly important pathological changes associated with aging.