Faculty of Social Sciences (Health Sciences), Tampere University, Tampere, Finland.
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Epigenetics Chromatin. 2021 Jul 2;14(1):33. doi: 10.1186/s13072-021-00407-6.
Ageing displays clear sexual dimorphism, evident in both morbidity and mortality. Ageing is also associated with changes in DNA methylation, but very little focus has been on the sex chromosomes, potential biological contributors to the observed sexual dimorphism. Here, we sought to identify DNA methylation changes associated with ageing in the Y and X chromosomes, by utilizing datasets available in data repositories, comprising in total of 1240 males and 1191 females, aged 14-92 years.
In total, we identified 46 age-associated CpG sites in the male Y, 1327 age-associated CpG sites in the male X, and 325 age-associated CpG sites in the female X. The X chromosomal age-associated CpGs showed significant overlap between females and males, with 122 CpGs identified as age-associated in both sexes. Age-associated X chromosomal CpGs in both sexes were enriched in CpG islands and depleted from gene bodies and showed no strong trend towards hypermethylation nor hypomethylation. In contrast, the Y chromosomal age-associated CpGs were enriched in gene bodies, and showed a clear trend towards hypermethylation with age.
Significant overlap in X chromosomal age-associated CpGs identified in males and females and their shared features suggest that despite the uneven chromosomal dosage, differences in ageing-associated DNA methylation changes in the X chromosome are unlikely to be a major contributor of sex dimorphism in ageing. While age-associated CpGs showed good replication across datasets in the present study, only a limited set of previously reported age-associated CpGs were replicated. One contributor to the limited overlap are differences in the age range of individuals included in each data set. Further study is needed to identify biologically significant age-associated CpGs in the sex chromosomes.
衰老表现出明显的性别二态性，在发病率和死亡率上都有体现。衰老与 DNA 甲基化的变化有关，但很少关注性染色体，这些性染色体是观察到的性别二态性的潜在生物学贡献者。在这里，我们试图通过利用数据存储库中可用的数据集，在总共 1240 名男性和 1191 名女性中，识别与 Y 和 X 染色体衰老相关的 DNA 甲基化变化，这些个体的年龄为 14-92 岁。
我们总共在男性 Y 染色体上鉴定出 46 个与年龄相关的 CpG 位点，在男性 X 染色体上鉴定出 1327 个与年龄相关的 CpG 位点，在女性 X 染色体上鉴定出 325 个与年龄相关的 CpG 位点。X 染色体上与年龄相关的 CpG 位点在女性和男性之间有显著的重叠，有 122 个 CpG 位点在两性中都与年龄相关。两性 X 染色体上与年龄相关的 CpG 位点在 CpG 岛中富集，在基因体中减少，没有强烈的超甲基化或低甲基化趋势。相比之下，Y 染色体上与年龄相关的 CpG 位点在基因体中富集，并随着年龄的增长呈现出明显的超甲基化趋势。
在男性和女性的 X 染色体上鉴定出的与年龄相关的 CpG 位点有显著的重叠，以及它们的共同特征表明，尽管性染色体的剂量不均等，但 X 染色体上与衰老相关的 DNA 甲基化变化的差异不太可能是衰老性别二态性的主要贡献者。虽然本研究中在数据集之间，与年龄相关的 CpG 位点有较好的复制，但只有有限的一组先前报道的与年龄相关的 CpG 位点得到了复制。造成这种有限重叠的一个原因是每个数据集所包含的个体的年龄范围不同。需要进一步的研究来鉴定性染色体上有生物学意义的与年龄相关的 CpG 位点。
