Aging and Chronic Sun Exposure Cause Distinct Epigenetic Changes in Human Skin

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.

表观遗传变化（Epigenetic changes）被广泛认为在衰老进程中发挥关键作用，但支持这一假说的实验证据却相对匮乏。我们采用基于微阵列的分析（array-based analysis）技术，对人类皮肤样本的全基因组DNA甲基化（DNA methylation）模式进行检测，并探究衰老、慢性日晒以及组织间差异对甲基化模式的影响。研究结果显示，甲基化模式具有高度的组织特异性，且同一组织内的个体间差异极小。按年龄对数据进行分层分析后发现，老年个体的DNA呈现出特定的高甲基化模式，该模式仅影响不到1%的被分析标记位点。有趣的是，按日晒暴露情况进行分层分析则得到了截然不同的模式，呈现出显著的低甲基化趋势。综上，本研究明确了与年龄相关的DNA甲基化改变，并提示此类变化可能促成了皮肤衰老相关的表型变化。