端粒长度调控及端粒与衰老和疾病的关系

Regulation of telomere length and its relationship with aging and diseases

端粒是线性染色体末端的DNA-蛋白质结构,可保护染色体末端免于降解和融合。由于大多数体细胞中存在末端复制问题和端粒酶缺乏的固有限制性,端粒DNA随着细胞每次分裂而缩短。短端粒或功能失调的端粒可诱导持续的DNA损伤反应,从而触发细胞复制性衰老。端粒长度主要通过端粒酶和端粒替代延长途经2种端粒机制维持。此外,端粒DNA还会被转录,生成含有端粒重复序列的RNA(telomeric repeat-containing RNA,TERRA),积极参与端粒维持和染色体末端保护。端粒长度是一种复杂的遗传特征,受遗传、疾病和环境因素的影响。流行病学数据显示,端粒长度与衰老、癌症、端粒生物学疾病及多种衰老相关疾病之间存在不同程度的关联。随着端粒长度检测方法的不断发展,血细胞端粒长度作为人类衰老生物标志物和衰老相关疾病的危险因素得到了广泛研究,具有作为生物标志物的潜力。

Telomeres are DNA-protein structures at the ends of linear chromosomes,protecting chromosome ends from degradation and fusion.Due to the inherent limitations of the end-replication problem and the lack of telomerase in most somatic cells,telomere DNA shortens as cells divide.Short or dysfunctional telomeres can induce a persistent DNA damage response,which triggers replicative senescence.Telomere length is mainly maintained by two telomere maintenance mechanisms,telomerase or alternative lengthening of telomeres.Telomere DNA can be transcribed to generate telomeric repeat-containing RNAs(TERRA),which are actively involved in telomere maintenance and chromosome end protection.Telomere length,a complex hereditary trait,is influenced by genetic,diseases,and environmental factors.Epidemiological data shows an association with varying magnitudes between telomere length and aging,cancers,telomere biology disorders,and several age-related diseases.With the development of telomere length detection methods,telomere length in blood cells has been studied extensively as a biomarker of human aging and risk factor for age-related diseases,which hold potential as a biomarker.