随着年龄的增长,DNA甲基化的指数动态
Grant Dufek1, Guy Katriel2, Sagi Snir3
1Department of Molecular, Cell and Developmental Biology; University of California, Los Angeles, CA 90095, USA.
Journal of theoretical biology
|December 23, 2023
概括
DNA甲基化动态遵循指数轨迹,随着年龄的增长接近稳定状态. 这一发现突出了非线性模式,对于开发准确的衰老生物标志物至关重要.
科学领域:
- 表观遗传学和分子生物学
- 计算生物学和生物信息学
- 老年学和衰老研究研究.
背景情况:
- 基因甲基化和时间学年龄之间的关系已经得到了很好的证实,许多研究探讨了与年龄相关的甲基化变化和开发预测生物标志物.
- 然而,对控制甲基化时代动态的功能形式的全面理解仍然有限,需要进一步的理论和实证研究.
研究的目的:
- 开发一个理论框架来建模个别地点的DNA甲基化动态.
- 研究甲基化年龄动态的功能形式和所涉及时间尺度的异质性.
- 评估这些非线性动态对衰老生物标志物的发展的影响.
主要方法:
- 开发了一个理论框架,以模拟单个地点的DNA甲基化动态,预测指数趋同到稳定状态水平.
- 该模型与跟踪从出生到老年大脑中的DNA甲基化变化的数据集相匹配.
- 模拟用于模拟融合时间尺度中的异质性,并分析甲基化动态与年龄的功能形式.
主要成果:
- 这项研究表明,DNA甲基化水平在指数上趋于稳定状态.
- 这种指数趋同的时间尺度在不同的DNA位点中被发现是异质的.
- 整个系统的平均甲基化动态密切遵循指数轨迹,表明随着年龄的增长发生的一致变化模式.
结论:
- 基因甲基化可以被概念化为一个系统,通过指数过程从出生时的不平衡状态向年龄的平衡状态过渡.
- 考虑非线性动态对于基于与年龄相关的DNA甲基化变化准确的生物标志物开发至关重要.
- 随着年龄的增长,DNA甲基化变化的指数性质进一步支持了衰老作为一个固有的指数过程的概念,反映了死亡风险的增加.
相关概念视频
01:37Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
01:29Replication in Eukaryotes
13.8K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.8K
03:17Inheritance of Chromatin Structures
6.3K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.3K
02:32Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
01:17Phase II Reactions: Methylation Reactions
193
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
193
02:30Genomic Imprinting and Inheritance
34.5K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
34.5K