Skin differences based on age and chronicity of ultraviolet exposure: results from a gene expression profiling study
Skin differences based on age and chronicity of ultraviolet exposure: results from a gene expression profiling study
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DOI：
10.1111/j.1365-2133.2012.10860.x
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发表时间：
2012-06-01
影响因子：
10.3
通讯作者：
Binder, R. L.
中科院分区：
文献类型：
--
作者：
McGrath, J. A.;Robinson, M. K.;Binder, R. L.
皮肤老化是衰老不可避免的生理结果，但对个人健康和福祉的影响可能是显著的，因此已经做出了相当大的努力来了解皮肤老化的生物学和病理生理学，试图确定可能提供治疗干预和预防的新目标。目的本研究旨在确定年轻人和老年人、日晒皮肤和防晒皮肤之间基因表达水平的差异。方法使用HG-U133 Plus 2.0 Affymetrix基因芯片，从日晒和防晒部位的年轻皮肤和老年皮肤（各10个样本）中获得转录组数据。使用分层聚类、主题分析和相互作用映射对数据进行分析，以确定受调节的途径、过程和潜在的治疗目标。结果在基因芯片上的54 613个探针组中，2731个有显著性差异（P = 0.05），但我们注意到13 640个探针组在年轻手臂皮肤与老年手臂皮肤（光老化）之间有显著性差异，7215个探针组在年轻臀部与老年臀部（内在老化）之间有显著性差异。在这两种类型的衰老中，许多与脂质生物合成和表皮分化有关的基因表达减少，这些基因的功能与皮肤屏障的完整性和维持有关。促进氧化应激的基因表达增加和抗氧化防御的表达减少在两种类型的衰老中也很常见。内在衰老和光老化的差异主要表现在细胞外基质基因表达上，内在衰老时间质胶原基因表达减少，光老化时弹性组织基因表达增加。总的来说，这些数据确定了衰老皮肤的新生物标志物，特别是涉及蛋白酶、基质蛋白和炎症的异常。这些发现为基于对皮肤老化生物学的更好理解的治疗开发提供了新的和更具体的目标。
Background Skin ageing represents an inevitable physiological consequence of getting older but the impact on personal health and wellbeing can be significant, and therefore considerable efforts have been made to understand the biology and pathophysiology of skin ageing to try to identify new targets that might offer therapeutic intervention and prevention. Objectives This study was designed to identify differences at the gene expression level between young and old, sun-exposed and sun-protected skin. Methods We generated transcriptomic data from young and old skin from sun-exposed and sun-protected sites (10 samples of each) using HG-U133 Plus 2.0 Affymetrix GeneChips. The data were analysed using hierarchical clustering, theme analysis and interaction mapping to identify regulated pathways, processes and potential targets for therapy. Results With 54 613 probe sets on the GeneChip, 2731 significant differences would be expected by chance (at P = 0.05), but we noted that 13 640 probe sets were significantly different comparing young arm skin vs. older arm skin (photoageing), and 7215 probe sets were significant for the young buttock vs. older buttock comparison (intrinsic ageing). In both types of ageing there was reduced expression of many genes implicated in lipid biosynthesis and epidermal differentiation with functional relevance to skin barrier integrity and maintenance. Increased expression of genes contributing to oxidative stress and decreased expression of antioxidant defences were also common to both types of ageing. Differences between intrinsic ageing and photoageing were mainly noted in extracellular matrix gene expression with reduced expression of interstitial collagen genes in intrinsic ageing and increased expression of elastic tissue genes in photoageing. Conclusions Collectively, the data identified new biomarkers of aged skin, particularly involving abnormalities of proteases, matrix proteins and inflammation. These findings offer the prospect of new and more specific targets for therapeutic development based on an improved understanding of the biology of skin ageing.