基于单核转录学的人类大脑细胞类型特定的衰老时钟
Chandramouli Muralidharan1,2,3, Enikő Zakar-Polyák4,5,6, Anita Adami1
1Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, 221 84, Sweden.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 29, 2025
概括
科学家们使用人类大脑数据开发了特定细胞类型的转录性衰老时钟. 这些时钟准确地测量了不同脑细胞的生物衰老, 揭示了神经退行性疾病的改变.
科学领域:
- 神经科学
- 基因组学
- 老龄化研究
背景情况:
- 衰老是神经退行性疾病的主要危险因素.
- 了解特定细胞类型的大脑衰老至关重要,
研究的目的:
- 开发和验证特定于人类细胞类型的转录组衰老时钟.
- 研究人类大脑中特定细胞类型的衰老模式.
- 在神经退行性疾病中探索改变的衰老轨迹.
主要方法:
- 使用了死后人类前额叶皮层的单核RNA测序数据 (31名18-94岁的捐赠者).
- 在主要脑细胞类型上训练的转录基因衰老时钟.
- 在独立数据集上验证了时钟性能.
主要成果:
- 在不同细胞类型中鉴定出与衰老相关的显著转录基因变化,包括微质中的炎症基因上调.
- 时间表准确地预测了年龄, 并捕捉了生物相关途径.
- 在独立的数据集中证明了时钟的稳定性.
- 在阿尔茨海默病和精神分裂症患者中观察到特定细胞类型的衰老加速.
结论:
- 细胞类型特定的转录原子钟是测量人类大脑生物衰老的可行工具.
- 这些时钟可以识别神经退行性疾病的衰老轨迹.
- 这些发现突出了神经疾病中选择性脆弱性的潜在机制.
更多相关视频
相关概念视频
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...


