Wnuk Maciej, Lewinska Anna, Gurgul Artur, Zabek Tomasz, Potocki Leszek, Oklejewicz Bernadetta, Bugno-Poniewierska Monika, Wegrzyn Magdalena, Slota Ewa
Department of Genetics, University of Rzeszów, Rejtana 16C, PL 35-959, Rzeszów, Poland,
Age (Dordr). 2014 Feb;36(1):31-48. doi: 10.1007/s11357-013-9541-z. Epub 2013 May 23.
It is known that aged organisms have modified epigenomes. Epigenetic modifications, such as changes in global and locus-specific DNA methylation, and histone modifications are suspected to play an important role in cancer development and aging. In the present study, with the well-established horse aging model, we showed the global loss of DNA methylation in blood lymphocytes during juvenile-to-aged period. Additionally, we tested a pattern of DNA methylation of ribosomal DNA and selected genes such as IGF2 and found no significant changes during development and aging. We asked if genetic components such as polymorphisms within DNA methyltransferase genes, DNMT1, DNMT3a, and DNMT3b, may contribute to observed changes in global DNA methylation status. The analysis of seven intragenic polymorphisms did not reveal any significant association with changes in global DNA methylation. Telomere shortage and a loss of pericentromeric heterochromatin during juvenile-to-aged period were also observed. Transcriptional rDNA activity, assessed as the number and size of nucleolar organizer regions, reflecting physiological state of the cell, and mitotic index were decreased with increasing horse donor age. Moreover, changes during juvenile-to-aged period and adult-to-aged period were compared and discussed. Taken together, changes in global DNA methylation status originating in development and affecting the stability of repetitive sequences may be associated with previously reported genomic instability during horse aging.
已知衰老生物体的表观基因组会发生改变。表观遗传修饰，如全基因组和基因座特异性DNA甲基化的变化以及组蛋白修饰，被怀疑在癌症发展和衰老过程中起重要作用。在本研究中，利用成熟的马衰老模型，我们展示了从幼年到老年阶段血液淋巴细胞中DNA甲基化的整体缺失。此外，我们检测了核糖体DNA以及IGF2等选定基因的DNA甲基化模式，发现在发育和衰老过程中没有显著变化。我们询问DNA甲基转移酶基因DNMT1、DNMT3a和DNMT3b内的多态性等遗传成分是否可能导致观察到的全基因组DNA甲基化状态变化。对七个基因内多态性的分析未发现与全基因组DNA甲基化变化有任何显著关联。在从幼年到老年阶段还观察到端粒缩短和着丝粒周围异染色质的缺失。作为核仁组织区数量和大小评估的转录性核糖体DNA活性反映了细胞的生理状态，并且随着马供体年龄的增加有丝分裂指数降低。此外，还比较和讨论了从幼年到老年阶段以及从成年到老年阶段的变化。综上所述，起源于发育并影响重复序列稳定性的全基因组DNA甲基化状态变化可能与先前报道的马衰老过程中的基因组不稳定性有关。
