在哺乳动物衰老过程中,全身细胞动态和表观基因组重塑
bioRxiv : the preprint server for biology
|June 4, 2025
概括
这项研究在21种组织中绘制了衰老过程中的细胞和表观基因组变化图,揭示了免疫细胞和特定器官群体的变化. 这些发现突出了衰老和性别差异的分子驱动因素,为治疗策略提供了洞察力.
科学领域:
- 老年学和分子生物学
- 基因组学和表观基因组学
- 细胞生物学 细胞生物学
背景情况:
- 衰老通过细胞和分子变化导致组织功能障碍.
- 需要对与年龄相关的细胞类型和表观基因组动态进行全面的目录.
研究的目的:
- 创建一个单细胞染色质可访问性地图,跨多种组织和年龄.
- 识别细胞群和表观基因组景观中与年龄相关的变化.
- 探索衰老动态中的依赖性差异.
主要方法:
- 从21种组织类型和3个年龄组的700万个细胞生成了一个单细胞染色质可访问性地图.
- 根据染色体的可访问性定义了536种主要细胞类型和1828种亚型.
- 分析了表观基因组的变化,转录因子的使用和细胞因子签名.
主要成果:
- 确定了广泛的免疫系重塑 (血细胞/巨细胞增加,T/B祖先减少).
- 在特定的非免疫细胞 (podocytes,粒状细胞,tenocytes,aerocytes) 中观察到与年龄相关的减少.
- 发现了成千上万的差异可访问的基因组区域,炎症和发育基因经常发生变化; ~40%的变化取决于性别.
结论:
- 衰老深刻地重塑细胞组成和多种组织的染色质可访问性.
- 跨器官的同步变化表明系统影响,如炎症或荷尔蒙.
- 这本地图集为了解衰老机制和开发有针对性的疗法提供了资源.
相关概念视频
Aging
40
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
40
Epigenetic 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
Mitochondria
11.7K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
11.7K
Nucleosome Remodeling
9.1K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.1K
PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
Telomeres and Telomerase
5.1K
5.1K


