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

摘要

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. Author Summary 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.