DNA methylation (DNAm) age constitutes a powerful tool to assess the molecular age and overall health status of biological samples. Recently, it has been shown that tissue-specific DNAm age predictors may present superior performance compared to the pan- or multi-tissue counterparts. The skin is the largest organ in the body and bears important roles, such as body temperature control, barrier function, and protection from external insults. As a consequence of the constant and intimate interaction between the skin and the environment, current DNAm estimators, routinely trained using internal tissues which are influenced by other stimuli, are mostly inadequate to accurately predict skin DNAm age. In the present study, we developed a highly accurate skin-specific DNAm age predictor, using DNAm data obtained from 508 human skin samples. Based on the analysis of 2,266 CpG sites, we accurately calculated the DNAm age of cultured skin cells and human skin biopsies. Age estimation was sensitive to the biological age of the donor, cell passage, skin disease status, as well as treatment with senotherapeutic drugs. This highly accurate skin-specific DNAm age predictor constitutes a holistic tool that will be of great use in the analysis of human skin health status/molecular aging, as well as in the analysis of the potential of established and novel compounds to alter DNAm age.

中文翻译：

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高度准确的皮肤特异性甲基化组分析算法作为筛选和验证健康衰老疗法的平台。

DNA 甲基化 (DNAm) 年龄是评估生物样本分子年龄和整体健康状况的有力工具。最近，已经表明，与泛组织或多组织对应物相比，组织特异性 DNAm 年龄预测因子可能具有更好的性能。皮肤是人体最大的器官，承担着重要的角色，如体温控制、屏障功能和保护免受外部伤害。由于皮肤和环境之间持续和密切的相互作用，目前的 DNAm 估计器通常使用受其他刺激影响的内部组织进行训练，大多不足以准确预测皮肤 DNAm 年龄。在本研究中，我们使用从 508 个人类皮肤样本中获得的 DNAm 数据开发了一种高度准确的皮肤特异性 DNAm 年龄预测器。基于对 2,266 个 CpG 位点的分析，我们准确计算了培养的皮肤细胞和人体皮肤活检组织的 DNAm 年龄。年龄估计对供体的生物学年龄、细胞传代、皮肤疾病状态以及使用老年治疗药物的治疗很敏感。这种高度准确的皮肤特异性 DNAm 年龄预测器构成了一个整体工具，将在分析人类皮肤健康状况/分子老化以及分析已建立和新型化合物改变 DNAm 年龄的潜力方面发挥重要作用。