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运动通过改变DNA来改善健康 精选
2021-8-3 09:09
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运动通过改变DNA来改善健康

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Figure 1. Identification of genes regulated by exercise training in human skeletal muscle.

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Figure 2. H3K4me1 and H3K27ac ChIP-seq identify enhancers that are regulated after exercise training.

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Figure 3. Association between exercise-training responsive enhancers and expression of connected genes. 

据丹麦哥本哈根大学健康与医学科学院 University of Copenhagen, Faculty of Health and Medical Sciences202182日提供的消息,由丹麦哥本哈根大学和瑞典卡罗琳斯卡医学院(Karolinska Institutet)以及卡罗琳斯卡大学医院(Karolinska University Hospital)的研究人员合作研究发现,运动是通过改变 DNA来改善健康的。

虽然众所周知,定期体育锻炼可以降低几乎所有慢性疾病的风险,但其作用机制尚不完全清楚。现在,哥本哈根大学与卡罗琳斯卡的科学家们发现,体育锻炼的有益效果可能部分源于我们DNA结构的变化,这些变化被称为表观遗传” 

DNA是我们所有细胞中的分子指导手册。我们DNA的某些部分是基因,它们是构建蛋白质(身体的组成部分)的指令,而其他部分被称为增强子(enhancers),用于调节哪些基因在何时以及在哪个组织中开启或关闭。科学家们首次发现,运动会重新连接我们已知与患病风险相关的DNA区域中的增强子。相关研究结果于2021710日已经在 《分子新陈代谢》(Molecular Metabolism)杂志网站发表——Kristine Williams, Germán D. Carrasquilla, Lars RoedIngerslev, Mette Yde Hochreuter, Svenja Hansson, Nicolas J. Pillon, Ida Donkin, Soetkin Versteyhe, Juleen R. Zierath, Tuomas O. Kilpeläinen, Romain Barrès. Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health. Molecular Metabolism, Available online 10 July 2021, 101290. DOI: 10.1016/j.molmet.2021.101290https://doi.org/10.1016/j.molmet.2021.101290

该研究的通讯作者、诺和诺德基金会基础代谢研究中心(Novo Nordisk Foundation Center for Basic Metabolic Research)的 Romain Barrès 教授说:“我们的研究结果为运动的已知有益效果提供了一种机制。通过将每个增强子与一个基因连接起来,我们进一步提供了一系列可以介导这种效应的直接目标。

运动可以改善包括大脑在内的器官健康(Exercise improves health of organs including the brain

科学家小组假设耐力运动训练重塑了骨骼肌中基因增强子的活动。他们招募了健康的年轻人,并让他们进行了为期六周的耐力锻炼计划。科学家们在运动干预前后收集了他们大腿肌肉的活检,并检查了他们的DNA表观遗传特征是否在训练后发生了变化。

科学家们发现,在完成耐力训练计划后,年轻人骨骼肌中许多增强子的结构发生了变化。通过将增强子连接到遗传数据库,他们发现许多受调控的增强子已经被确定为个体之间遗传变异的热点——与人类疾病相关的热点。

科学家们推测,运动对远离肌肉的器官(如大脑)的有益影响可能主要是通过调节肌肉因子(muscle factors)的分泌来介导的。特别是,他们发现运动可以重塑与认知能力相关的骨骼肌中的增强子活动,这为识别运动训练诱导的针对大脑的分泌肌肉因子打开了大门。

我们的数据提供了增强子表观遗传重新布线以控制运动训练后其活动与人类疾病风险调节之间的功能联系的证据,该研究的主要作者克里斯汀·威廉姆斯(Kristine Williams)助理教授说。上述介绍,仅供参考。欲了解更多信息敬请注意浏览原文或者相关报道

New insight into how muscles and fat cells work together to make you more fit

Highlights

• Exercise training changes in skeletal muscle gene expression is enriched for secreted factors.

• The activity of skeletal muscle enhancers undergoes substantial remodeling after exercise training.

• Skeletal muscle enhancer activity and gene transcription are strongly associated.

• Exercise training-remodeled enhancer regions are enriched for GWAS SNPs associated with human traits and diseases.

Abstract

Objectives

Regular physical exercise improves health by reducing the risk of a plethora of chronic disorders. We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health.

Methods and results

By studying changes in histone modifications, we mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary men before and after 6 weeks of endurance exercise. We identified extensive remodeling of enhancer activities after exercise training, with a large subset of the remodeled enhancers located in the proximity of genes transcriptionally regulated after exercise. By overlapping the position of enhancers with genetic variants, we identified an enrichment of disease-associated genetic variants within the exercise-remodeled enhancers.

Conclusion

Our data provide evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans.


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