Kuehne Andreas, Hildebrand Janosch, Soehle Joern, Wenck Horst, Terstegen Lara, Gallinat Stefan, Knott Anja, Winnefeld Marc, Zamboni Nicola
Institute of Molecular Systems Biology, ETH Zurich, Auguste-Piccard-Hof 1, 8093, Zürich, Switzerland.
PhD Program Systems Biology, Life Science Zurich Graduate School, Zurich, Switzerland.
BMC Genomics. 2017 Feb 15;18(1):169. doi: 10.1186/s12864-017-3547-3.
Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders.
We investigated the global metabolic adaptions in human skin during aging with a combined transcriptomic and metabolomic approach applied to epidermal tissue samples of young and old human volunteers. Our analysis confirmed known age-dependent metabolic alterations, e.g. reduction of coenzyme Q10 levels, and also revealed novel age effects that are seemingly important for skin maintenance. Integration of donor-matched transcriptome and metabolome data highlighted transcriptionally-driven alterations of metabolism during aging such as altered activity in upper glycolysis and glycerolipid biosynthesis or decreased protein and polyamine biosynthesis. Together, we identified several age-dependent metabolic alterations that might affect cellular signaling, epidermal barrier function, and skin structure and morphology.
Our study provides a global resource on the metabolic adaptations and its transcriptional regulation during aging of human skin. Thus, it represents a first step towards an understanding of the impact of metabolism on impaired skin function in aged humans and therefore will potentially lead to improved treatments of age related skin disorders.
衰老的人类皮肤会经历显著的形态和功能变化,如皱纹形成、伤口愈合能力下降以及表皮屏障功能改变。除了已知的与年龄相关的变化,如DNA甲基化改变外,代谢适应最近还被认为与老年人皮肤功能受损有关。了解老年皮肤中的这些代谢适应对于设计可能逆转或减轻年龄依赖性皮肤恶化和皮肤疾病发生的局部治疗方法具有特殊意义。
我们采用转录组学和代谢组学相结合的方法,对年轻和老年人类志愿者的表皮组织样本进行分析,以研究衰老过程中人类皮肤的整体代谢适应情况。我们的分析证实了已知的与年龄相关的代谢改变,如辅酶Q10水平降低,还揭示了一些对皮肤维持似乎很重要的新的年龄效应。将供体匹配的转录组和代谢组数据整合在一起,突出了衰老过程中由转录驱动的代谢改变,如糖酵解上游和甘油脂质生物合成活性改变,或蛋白质和多胺生物合成减少。我们共同确定了几种可能影响细胞信号传导、表皮屏障功能以及皮肤结构和形态的与年龄相关的代谢改变。
我们的研究提供了关于人类皮肤衰老过程中代谢适应及其转录调控的全面资源。因此,它代表了迈向理解代谢对老年人类皮肤功能受损影响的第一步,有望改善对与年龄相关皮肤疾病的治疗。