Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095, USA.
Aging (Albany NY). 2024 Jul 9;16(13):10724-10748. doi: 10.18632/aging.206012.
Chronological age reveals the number of years an individual has lived since birth. By contrast, biological age varies between individuals of the same chronological age at a rate reflective of physiological decline. Differing rates of physiological decline are related to longevity and result from genetics, environment, behavior, and disease. The creation of methylation biological age predictors is a long-standing challenge in aging research due to the lack of individual longevity data. The consistent differences in longevity between domestic dog breeds enable the construction of biological age estimators which can, in turn, be contrasted with methylation measurements to elucidate mechanisms of biological aging. We draw on three flagship methylation studies using distinct measurement platforms and tissues to assess the feasibility of creating biological age methylation clocks in the dog. We expand epigenetic clock building strategies to accommodate phylogenetic relationships between individuals, thus controlling for the use of breed standard metrics. We observe that biological age methylation clocks are affected by population stratification and require heavy parameterization to achieve effective predictions. Finally, we observe that methylation-related markers reflecting biological age signals are rare and do not colocalize between datasets.
年龄揭示了一个人自出生以来所经历的年数。相比之下，生物年龄在同一年龄的个体之间存在差异，其变化速度反映了生理衰退的速度。不同的生理衰退速度与寿命有关，是由遗传、环境、行为和疾病等因素决定的。由于缺乏个体长寿数据，因此创建甲基化生物年龄预测模型一直是衰老研究中的一个长期挑战。由于不同犬种之间存在着明显的寿命差异，因此可以构建生物年龄估算模型，然后将其与甲基化测量结果进行对比，以阐明生物衰老的机制。我们借鉴了三项使用不同检测平台和组织的旗舰甲基化研究，以评估在犬类中创建生物年龄甲基化时钟的可行性。我们扩展了表观遗传时钟构建策略，以适应个体之间的系统发育关系，从而控制使用品种标准指标。我们观察到生物年龄甲基化时钟受群体分层的影响，并且需要大量参数化才能实现有效的预测。最后，我们观察到反映生物年龄信号的与甲基化相关的标记物很少，并且在不同数据集之间没有共定位。
