Ageing Research Reviews ( IF 13.1 ) Pub Date : 2020-06-18 , DOI: 10.1016/j.arr.2020.101115 Julio Aguado 1 , Fabrizio d'Adda di Fagagna 2 , Ernst Wolvetang 1
Telomeres, the ends of eukaryotic chromosomes, play a central role in the control of cellular senescence and organismal ageing and need to be protected in order to avoid being recognised as damaged DNA and activate DNA damage response pathways. Dysfunctional telomeres arise from critically short telomeres or altered telomere structures, which ultimately lead to replicative cellular senescence and chromosome instability: both hallmarks of ageing. The observation that telomeres are transcribed led to the discovery that telomeric transcripts play important roles in chromosome end protection and genome stability maintenance. Recent evidence indicates that particular long non-coding (nc)RNAs transcribed at telomeres, namely TElomeric Repeat-containing RNA (TERRA) and telomeric damage-induced long ncRNAs (tdilncRNA), play key roles in age-related pathways by actively orchestrating the mechanisms known to regulate telomere length, chromosome end protection and DNA damage signalling. Here, we provide a comprehensive overview of the telomere transcriptome, outlining how it functions as a regulatory platform with essential functions in safeguarding telomere integrity and stability. We next review emerging antisense oligonucleotides therapeutic strategies that target telomeric ncRNAs and discuss their potential for ameliorating ageing and age-related diseases. Altogether, this review provides insights on the biological relevance of telomere transcription mechanisms in human ageing physiology and pathology.
中文翻译:
端粒转录老化。
端粒是真核染色体的末端,在控制细胞衰老和机体衰老中起着核心作用,需要加以保护,以避免被识别为受损的DNA并激活DNA损伤反应途径。功能失调的端粒源于严重的端粒短促或端粒结构改变,最终导致复制性细胞衰老和染色体不稳定:这都是衰老的标志。对端粒转录的观察导致发现端粒转录物在染色体末端保护和基因组稳定性维持中起重要作用。最近的证据表明,特定的长非编码(nc)RNA在端粒转录,即端粒重复序列含RNA(TERRA)和端粒损伤诱导的长ncRNA(tdilncRNA),通过积极协调已知的调节端粒长度,染色体末端保护和DNA损伤信号转导的机制,在与年龄相关的途径中发挥关键作用。在这里,我们提供端粒转录组的全面概述,概述端粒转录组如何作为具有维护端粒完整性和稳定性的基本功能的调控平台。接下来,我们将综述针对端粒ncRNA的新兴反义寡核苷酸治疗策略,并讨论其改善衰老和与年龄有关的疾病的潜力。总之,这篇综述提供了关于端粒转录机制在人类衰老生理学和病理学中的生物学意义的见解。我们提供了端粒转录组的全面概述,概述了端粒转录组如何作为具有维护端粒完整性和稳定性的基本功能的调控平台而发挥作用。接下来,我们将综述针对端粒ncRNA的新兴反义寡核苷酸治疗策略,并讨论其改善衰老和与年龄有关的疾病的潜力。总之,这篇综述提供了关于端粒转录机制在人类衰老生理学和病理学中的生物学意义的见解。我们提供了端粒转录组的全面概述,概述了端粒转录组如何作为具有维护端粒完整性和稳定性的基本功能的调控平台而发挥作用。接下来,我们将综述针对端粒ncRNA的新兴反义寡核苷酸治疗策略,并讨论其改善衰老和与年龄有关的疾病的潜力。总之,这篇综述提供了关于端粒转录机制在人类衰老生理学和病理学中的生物学意义的见解。接下来,我们将综述针对端粒ncRNA的新兴反义寡核苷酸治疗策略,并讨论其改善衰老和与年龄有关的疾病的潜力。总之,这篇综述提供了关于端粒转录机制在人类衰老生理学和病理学中的生物学意义的见解。接下来,我们将综述针对端粒ncRNA的新兴反义寡核苷酸治疗策略,并讨论其改善衰老和与年龄有关的疾病的潜力。总之,这篇综述提供了关于端粒转录机制在人类衰老生理学和病理学中的生物学意义的见解。