Research & Development, Beiersdorf AG, Hamburg, Germany.
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
Exp Dermatol. 2024 Oct;33(10):e70005. doi: 10.1111/exd.70005.
Skin aging is driven by a complex set of cellular pathways. Among these, epigenetic mechanisms have garnered particular attention, because of their sensitivity to environmental and lifestyle factors. DNA methylation represents the longest known and best understood epigenetic mechanism. We explain how DNA methylation might function as an interface between the environment and the genome of human skin. Exposures to different environmental factors and lifestyles are known to modulate age-related methylation patterns, as illustrated by their effect on DNA methylation clocks. Human skin provides a particularly well-suited tissue for understanding age-related methylation changes and it has been shown recently that modulation of DNA methylation can induce skin rejuvenation. We explain how the use of mildly demethylating agents can be safeguarded to ensure the specific removal of age-related DNA methylation changes. We also identify important areas of future research, leading to a deeper understanding of the mechanisms that drive epigenetic aging and to the development of further refined intervention strategies.
皮肤老化是由一系列复杂的细胞通路驱动的。在这些通路中，表观遗传机制引起了特别的关注，因为它们对环境和生活方式因素敏感。DNA 甲基化是已知的最长且最被理解的表观遗传机制。我们解释了 DNA 甲基化如何作为环境和人类皮肤基因组之间的接口发挥作用。已知不同的环境因素和生活方式的暴露会调节与年龄相关的甲基化模式，这可以通过它们对 DNA 甲基化时钟的影响来说明。人类皮肤是一种特别适合用于理解与年龄相关的甲基化变化的组织，最近已经表明，DNA 甲基化的调节可以诱导皮肤年轻化。我们解释了如何使用轻度去甲基化剂来确保特异性地去除与年龄相关的 DNA 甲基化变化。我们还确定了未来研究的重要领域，以深入了解驱动表观遗传衰老的机制，并开发进一步精细化的干预策略。
