Maierhofer Anna, Flunkert Julia, Oshima Junko, Martin George M, Haaf Thomas, Horvath Steve
Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
Department of Pathology, University of Washington, Seattle, WA 98105, USA.
Aging (Albany NY). 2017 Apr;9(4):1143-1152. doi: 10.18632/aging.101217.
Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.
患有沃纳综合征（WS）的个体表现出许多加速衰老的临床症状。虽然潜在的体质性突变会导致DNA损伤速率加快，但根据基于DNA甲基化的衰老生物标志物（“表观遗传时钟”），WS是否也与表观遗传年龄增加有关尚不清楚。利用18例WS患者和18例年龄匹配的对照的全血甲基化数据，我们发现WS与外在表观遗传年龄加速增加（p = 0.0072）和内在表观遗传年龄加速增加（p = 0.04）有关，后者独立于外周血细胞组成的年龄相关变化。多变量模型分析显示，即使在调整了实际年龄、性别和血细胞计数后，WS仍与DNA甲基化年龄增加有关（平均6.4岁，p = 0.011）。此外，根据估算的血细胞计数测量，WS可能与幼稚CD８+T细胞减少有关（p = 0.025）。总体而言，本研究表明WS与血细胞表观遗传年龄增加有关，且独立于血细胞组成的变化。这种改变在多大程度上是WS疾病表型的原因或结果尚不清楚。
