Department of Anthropology, University of North Carolina Wilmington, Wilmington, NC, USA.
Department of Anthropology and Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, DC, USA.
Epigenetics. 2022 Dec;17(12):1774-1785. doi: 10.1080/15592294.2022.2080993. Epub 2022 Jun 2.
Epigenetic age has emerged as an important biomarker of biological ageing. It has revealed that some tissues age faster than others, which is vital to understanding the complex phenomenon of ageing and developing effective interventions. Previous studies have demonstrated that humans exhibit heterogeneity in pace of epigenetic ageing among brain structures that are consistent with differences in structural and microanatomical deterioration. Here, we add comparative data on epigenetic brain ageing for chimpanzees, humans' closest relatives. Such comparisons can further our understanding of which aspects of human ageing are evolutionarily conserved or specific to our species, especially given that humans are distinguished by a long lifespan, large brain, and, potentially, more severe neurodegeneration with age. Specifically, we investigated epigenetic ageing of the dorsolateral prefrontal cortex and cerebellum, of humans and chimpanzees by generating genome-wide CpG methylation data and applying established epigenetic clock algorithms to produce estimates of biological age for these tissues. We found that both species exhibit relatively slow epigenetic ageing in the brain relative to blood. Between brain structures, humans show a faster rate of epigenetic ageing in the dorsolateral prefrontal cortex compared to the cerebellum, which is consistent with previous findings. Chimpanzees, in contrast, show comparable rates of epigenetic ageing in the two brain structures. Greater epigenetic change in the human dorsolateral prefrontal cortex compared to the cerebellum may reflect both the protracted development of this structure in humans and its greater age-related vulnerability to neurodegenerative pathology.
表观遗传年龄已成为生物衰老的一个重要生物标志物。它揭示了一些组织的衰老速度比其他组织快，这对于理解衰老的复杂现象和开发有效的干预措施至关重要。先前的研究表明，人类在大脑结构中的表观遗传衰老速度存在异质性，这与结构和微观解剖恶化的差异一致。在这里，我们为人类最亲近的亲属黑猩猩添加了关于大脑表观遗传衰老的比较数据。这种比较可以进一步了解哪些方面的人类衰老在进化上是保守的，或者是我们物种特有的，特别是因为人类的寿命长、大脑大，而且随着年龄的增长，神经退行性变可能更严重。具体来说，我们通过生成全基因组 CpG 甲基化数据并应用既定的表观遗传时钟算法来产生这些组织的生物年龄估计值，研究了人类和黑猩猩的背外侧前额叶皮层和小脑的表观遗传衰老。我们发现，与血液相比，这两个物种的大脑都表现出相对较慢的表观遗传衰老。在大脑结构之间，与小脑相比，人类的背外侧前额叶皮层表现出更快的表观遗传衰老速度，这与先前的发现一致。相比之下，黑猩猩在这两个大脑结构中表现出相似的表观遗传衰老速度。与小脑相比，人类背外侧前额叶皮层的表观遗传变化更大，这可能反映了该结构在人类中的发育过程较长，以及其在衰老相关神经退行性病理方面的更大脆弱性。
