表观遗传时钟 性染色体的分析 性染色体积症
Joshua Zhang1, Jordan Teoli2,3,4,5, Benjamin Rey4
1Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, USA.
Aging cell
|September 30, 2025
概括
性染色体剂量影响表观遗传衰老. 额外的X染色体 (47,XXY) 在较新的DNA甲基化钟表中表现出较慢的衰老,但在较旧的钟表中表现出更快的衰老,揭示出明显的生物衰老措施.
科学领域:
- 遗传学 是一个遗传学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 衰老研究研究 衰老研究
背景情况:
- 寿命的性别差异很常见,但性染色体在DNA甲基化 (DNAm) 相关的衰老中的作用尚不清楚.
- 人类性染色体形状提供了一个独特的模型来研究X和Y染色体剂量对衰老的影响.
研究的目的:
- 为了研究X和Y染色体剂量如何影响表观遗传衰老,使用DNA甲基化 (DNAm) 时钟.
- 为了比较第一代和下一代DNAm时钟在具有不同性染色体补充的个体中的性能.
主要方法:
- 表观遗传年龄和年龄加速被测量在46,XX,46,XY,47,XXY和47,XYY类型的个体的全血中.
- 使用了三个DNAm时钟:皮肤和血液 (第一代),GrimAge和DunedinPACE (下一代).
- 分析了GrimAge和自体表观遗传广泛关联研究 (EWAS) 位点的组成部分.
主要成果:
- 下一代时钟 (GrimAge,DunedinPACE) 在47,XXY中显示出较低的年龄加速和较慢的衰老速度,与46,XY相比.
- 特定的DNAm标记物 (DNAmLeptin,DNAmPACKYRS) 在47,XXY.中降低了GrimAge.
- 第一个代的皮肤和血液时钟在47,XXY和47,XYY中显示了较高的年龄加速,与46,XY相比.
- EWAS突出显示了免疫路径和型特异性特征 (代谢/癌症为47,XXY;脏/氨基酸为47,XYY).
结论:
- X染色体的增加 (47,XXY) 与GrimAge和DunedinPACE的表观遗传衰老减少有关,但皮肤和血液时钟的衰老增加.
- 不同的DNAm时钟捕捉了由性染色体剂量影响的独特的生物衰老方面.
- 需要对更大的队列和直接表型进行进一步的研究,以阐明机制.
相关概念视频
Nondisjunction
4.8K
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
4.8K
Nondisjunction
81.8K
During meiosis, chromosomes occasionally separate improperly. This occurs due to failure of homologous chromosome separation during meiosis I or failed sister chromatid separation during meiosis II. In some species, notably plants, nondisjunction can result in an organism with an entire additional set of chromosomes, which is called polyploidy. In humans, nondisjunction can occur during male or female gametogenesis and the resulting gametes possess one too many or one too few chromosomes.
81.8K
The Ratio of X Chromosome to Autosomes
9.4K
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female...
9.4K
X and Y Chromosomes
29.4K
Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
29.4K
Inheritance of Chromatin Structures
7.3K
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...
7.3K
Meiosis I
43.8K
Meiosis is the division of a diploid cell into haploid cells forming sperm and eggs in animals through differentiation. Meiosis I is the first stage of meiosis, where the genetic recombination of homologous chromosomes and the reduction of the ploidy level by half occurs.
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
43.8K


