Aging and chronic sun exposure cause distinct epigenetic changes in human skin.
Aging and chronic sun exposure cause distinct epigenetic changes in human skin.
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DOI：
10.1371/journal.pgen.1000971
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发表时间：
2010-05-27
期刊：
影响因子：
4.5
通讯作者：
Lyko F
中科院分区：
文献类型：
--
作者：
Grönniger E;Weber B;Heil O;Peters N;Stäb F;Wenck H;Korn B;Winnefeld M;Lyko F
表观遗传变化被广泛认为在衰老中起重要作用，但支持这一假设的实验证据很少。我们使用基于阵列的分析来确定人类皮肤样本的基因组尺度DNA甲基化模式，并研究衰老、长期阳光照射和组织变异的影响。我们的研究结果揭示了甲基化模式的高度组织特异性，并且在组织内也显示了非常小的个体间差异。按年龄分层的数据显示，来自老年人的DNA具有特定的超甲基化模式，影响不到1%的分析标记。有趣的是，阳光照射的分层产生了一种根本不同的模式，具有显著的低甲基化趋势。因此，我们的研究结果确定了与年龄相关的DNA甲基化变化，并表明这些变化可能有助于与皮肤衰老相关的表型变化。尽管表观遗传机制在衰老和对环境暴露的适应中起着广泛的作用，但这一领域的研究一直受到主要方法挑战的阻碍。我们现在已经使用了一种新的基因组尺度甲基化分析平台来确定人类皮肤样本的甲基化模式。皮肤代表了一个特别适合这项研究的模型，因为它众所周知的与衰老和阳光照射相关的表型变化，因为皮肤样本的特征是高度的细胞同质性。通过检查50个样本，分析5000万个数据点，我们发现衰老和阳光照射与人类表皮和真皮样本DNA甲基化模式的相对较小但显著的变化有关。有趣的是，衰老与DNA甲基化模式的一般变化无关，而是与定向的DNA超甲基化转移有关。重要的是，我们的研究结果还表明，表观遗传机制可能在与衰老和慢性阳光照射相关的表型变化中具有重要的功能。
Epigenetic changes are widely considered to play an important role in aging, but experimental evidence to support this hypothesis has been scarce. We have used array-based analysis to determine genome-scale DNA methylation patterns from human skin samples and to investigate the effects of aging, chronic sun exposure, and tissue variation. Our results reveal a high degree of tissue specificity in the methylation patterns and also showed very little interindividual variation within tissues. Data stratification by age revealed that DNA from older individuals was characterized by a specific hypermethylation pattern affecting less than 1% of the markers analyzed. Interestingly, stratification by sun exposure produced a fundamentally different pattern with a significant trend towards hypomethylation. Our results thus identify defined age-related DNA methylation changes and suggest that these alterations might contribute to the phenotypic changes associated with skin aging. Although a role of epigenetic mechanisms in aging and in the adaptation to environmental exposures has been widely assumed, research in this area has been hampered by major methodological challenges. We have now used a novel platform for genome-scale methylation analysis to determine the methylation patterns of human skin samples. Skin represents a particularly suitable model for this study because of its well-known phenotype changes associated with aging and sun exposure, and because skin samples are characterized by a very high degree of cellular homogeneity. By examining 50 samples, and analyzing 50 million data points, we show that aging and sun exposure are associated with comparably small, but significant changes in the DNA methylation patterns of human epidermis and dermis samples. Interestingly, aging was not associated with a general variation in DNA methylation patterns, but rather with a directed DNA hypermethylation shift. Importantly, our results also suggest that epigenetic mechanisms may be functionally important for the phenotypic changes associated with aging and chronic sun exposure.
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影响因子：
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作者：
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