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首页> 外文期刊>Clinical epigenetics. >Insufficient DNA methylation affects healthy aging and promotes age-related health problems
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Insufficient DNA methylation affects healthy aging and promotes age-related health problems

机译：DNA甲基化不足会影响健康的衰老并引发与年龄有关的健康问题

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DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/? mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dual-energy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.
机译：DNA甲基化通过基因组功能的表观遗传调控在发育和衰老中起着不可或缺的作用。 DNA甲基转移酶1（Dnmt1）是保持基因组甲基化稳定性最普遍的DNA甲基转移酶。为了进一步阐明Dnmt1在衰老和与年龄有关的疾病中的功能，我们开发了Dnmt1 + /?。小鼠模型，通过评估几种主要衰老表型的变化，研究Dnmt1单倍体不足对衰老过程的影响。我们证实，由于Dnmt1表达降低，Dnmt1单倍体不足确实会降低DNA甲基化。为了评估Dnmt1单倍剂量不足对一般人体成分的影响，我们进行了双能X线骨密度仪分析，结果表明Dnmt1活性降低会降低骨矿物质密度和体重，但对死亡率或体内脂肪含量没有明显影响。使用行为测试，我们证明了Dnmt1单倍体功能不足会以年龄相关的方式损害学习和记忆功能。综上所述，我们的发现指出了有趣的可能性，即降低的基因组甲基化活性会对健康的衰老过程产生不利影响，而不会改变生存率和死亡率。我们的研究表明，中枢神经系统的认知功能受到Dnmt1活性和基因组甲基化的调节，突显了记忆编码和功能背后的原始表观遗传学假设的重要性。

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