端粒酶通过维护和保护端粒来保持基因组完整性。1985年的开创性发现揭示了端粒酶的规范作用，并激发了对抗衰老的一个标志性因素——端粒消耗的潜在治疗策略的研究。自那时以来，端粒生物学领域迅速发展，端粒酶通过其规范功能在癌症和细胞发育中发挥重要作用。但是，端粒酶通过其蛋白质（端粒酶逆转录酶TERT）和RNA组分（端粒酶RNA组分TERC）也发挥着重要的非端粒作用。端粒酶的再活化或异位表达促进了肿瘤和健康非恶性细胞的生存和无限增殖。TERT基因疗法改善了老龄小鼠和老年相关疾病的小鼠模型中的健康和寿命。端粒酶的非端粒功能对于衰老是至关重要的。这些功能包括对抗氧化应激、协调染色质修饰和转录、以及对血管生成和代谢的调节（例如线粒体功能和葡萄糖控制）。考虑到这些生物学功能是耐力训练的关键适应性，并且最近的元分析发现运动上调TERT和端粒酶，这就需要对端粒酶的规范和非端粒作用的影响进行全面的讨论。本综述强调了端粒酶基因治疗用于与衰老有关的特发性和慢性疾病的治疗效益。讨论了端粒酶的规范和非端粒作用，接着详细总结了运动如何影响端粒酶的证据。最后，讨论了运动诱导的端粒酶调节的潜在细胞信号，同时探讨未来研究的方向。©2023作者。Anatomical Society和John Wiley＆Sons Ltd.出版的Aging Cell 发表。

Telomerase preserves genomic integrity by maintaining and protecting the telomeres. Seminal findings from 1985 revealed the canonical role of telomerase and motivated investigations into potential therapeutic strategies to combat one of the hallmarks of ageing-telomere attrition. Since then, the field of telomere biology has rapidly expanded, with telomerase serving essential roles in cancer and cell development through its canonical function. However, telomerase also exerts critical extra-telomeric functions through its protein (telomerase reverse transcriptase, TERT) and RNA components (telomerase RNA component, TERC). Telomerase re-activation or ectopic expression promotes survival and permits unlimited proliferation in tumours and healthy non-malignant cells. TERT gene therapies improve health and lifespan in ageing mice and mouse models of age-related diseases. The extra-telomeric functions of telomerase are critical to ageing. These include protection against oxidative stress, orchestration of chromatin modifications and transcription, and regulation of angiogenesis and metabolism (e.g. mitochondrial function and glucose control). Given these biological functions are key adaptations to endurance training and the recent meta-analytical findings that indicate exercise up-regulates TERT and telomerase, a comprehensive discussion on the implications of the canonical and extra-telomeric roles of telomerase is warranted. This review highlights the therapeutic benefits of telomerase-based treatments for idiopathic and chronic diseases that are linked to ageing. Discussion on the canonical and extra-telomeric roles of telomerase are presented, followed by a detailed summary of the evidence on how exercise influences telomerase. Finally, the potential cell signalling underpinning the exercise-induced modulation of telomerase are discussed with directions for future research.© 2023 The Author. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.