Bienkowska Agata, Raddatz Günter, Söhle Jörn, Kristof Boris, Völzke Henry, Gallinat Stefan, Lyko Frank, Kaderali Lars, Winnefeld Marc, Grönniger Elke, Falckenhayn Cassandra
Beiersdorf AG, Research and Development, Hamburg, Germany.
Institute for Bioinformatics, University Medicine Greifswald, Greifswald, Germany.
Front Aging. 2024 Jan 11;4:1258183. doi: 10.3389/fragi.2023.1258183. eCollection 2023.
Aging is a complex process characterized by the gradual decline of physiological functions, leading to increased vulnerability to age-related diseases and reduced quality of life. Alterations in DNA methylation (DNAm) patterns have emerged as a fundamental characteristic of aged human skin, closely linked to the development of the well-known skin aging phenotype. These changes have been correlated with dysregulated gene expression and impaired tissue functionality. In particular, the skin, with its visible manifestations of aging, provides a unique model to study the aging process. Despite the importance of epigenetic age clocks in estimating biological age based on the correlation between methylation patterns and chronological age, a second-generation epigenetic age clock, which correlates DNAm patterns with a particular phenotype, specifically tailored to skin tissue is still lacking. In light of this gap, we aimed to develop a novel second-generation epigenetic age clock explicitly designed for skin tissue to facilitate a deeper understanding of the factors contributing to individual variations in age progression. To achieve this, we used methylation patterns from more than 370 female volunteers and developed the first skin-specific second-generation epigenetic age clock that accurately predicts the skin aging phenotype represented by wrinkle grade, visual facial age, and visual age progression, respectively. We then validated the performance of our clocks on independent datasets and demonstrated their broad applicability. In addition, we integrated gene expression and methylation data from independent studies to identify potential pathways contributing to skin age progression. Our results demonstrate that our epigenetic age clock, VisAgeX, specifically predicting visual age progression, not only captures known biological pathways associated with skin aging, but also adds novel pathways associated with skin aging.
衰老是一个复杂的过程，其特征是生理功能逐渐衰退，导致对与年龄相关疾病的易感性增加以及生活质量下降。DNA甲基化（DNAm）模式的改变已成为老年人皮肤的一个基本特征，与众所周知的皮肤衰老表型的发展密切相关。这些变化与基因表达失调和组织功能受损有关。特别是，皮肤具有明显的衰老表现，为研究衰老过程提供了一个独特的模型。尽管表观遗传年龄时钟在基于甲基化模式与实际年龄之间的相关性来估计生物学年龄方面很重要，但专门针对皮肤组织、将DNAm模式与特定表型相关联的第二代表观遗传年龄时钟仍然缺乏。鉴于这一差距，我们旨在开发一种专门为皮肤组织设计的新型第二代表观遗传年龄时钟，以促进对导致个体年龄进展差异的因素有更深入的了解。为了实现这一目标，我们使用了370多名女性志愿者的甲基化模式，开发了第一个皮肤特异性第二代表观遗传年龄时钟，该时钟分别准确预测了由皱纹等级、面部视觉年龄和视觉年龄进展所代表的皮肤衰老表型。然后，我们在独立数据集上验证了我们的时钟的性能，并证明了它们的广泛适用性。此外，我们整合了来自独立研究的基因表达和甲基化数据，以确定有助于皮肤年龄进展的潜在途径。我们的结果表明，我们的表观遗传年龄时钟VisAgeX，专门预测视觉年龄进展，不仅捕捉到了与皮肤衰老相关的已知生物学途径，还增加了与皮肤衰老相关的新途径。
