BackgroundThe Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments.ResultsThe model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways.ConclusionsThe concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.

中文翻译：

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系统地低估老年受试者的表观遗传时钟和年龄加速

背景 Horvath 表观遗传时钟被广泛使用。它从未知样本中 DNA 甲基化谱中的 353 个 CpG 位点很好地预测了年龄，并已被用于计算各种组织和环境中的“年龄加速”。结果该模型系统地低估了老年人组织中的年龄。这在所有检查的组织中都可以看到，但在小脑中最强烈，并且在多个数据集中始终如一地观察到。因此，年龄加速与年龄有关，这可能导致虚假关联。目前的文献包括以多种方式计算的年龄加速关联测试的示例。结论表观遗传时钟的概念是令人信服的，但在解释与年龄加速的关联时应谨慎。年龄加速的关联测试应该包括年龄作为协变量。