端粒生物学最初在玉米、纤毛虫、酵母和小鼠中进行了研究，在最近几十年里，它已经为理解常见疾病机制提供了信息，对患者护理具有广泛的影响。短端粒综合征是最普遍的早衰性疾病，其显著表型影响肺和造血系统。较少为人所知的是，一类新近认识到的易患癌症综合征与伸长端粒的突变有关。大量新的孟德尔遗传学和流行病学数据现在提供了重新考虑端粒在人类衰老和癌症中作用范式的机会，在某些情况下，结果与模型系统的解释不同。例如，短端粒曾被认为是基因组不稳定性的强力驱动因素，但在具有短端粒综合征的个体中，年龄相关的实体瘤很少见，而T细胞免疫缺陷解释了它们的光谱。更普遍的是，短端粒促进克隆造血，包括体细胞逆转，提供了一个独立于基因组不稳定性的新的白血病发生范式。另一方面，在体外延长细胞寿命的长端粒现在被认为是人群研究中最常见的共享生殖系风险因素癌症。通过这个当代角度，我在这里重新审视端粒在人类衰老中的作用，重点是短和长端粒如何通过不同的机制推动癌症进化。

Telomere biology was first studied in maize, ciliates, yeast, and mice, and in recent decades, it has informed understanding of common disease mechanisms with broad implications for patient care. Short telomere syndromes are the most prevalent premature aging disorders, with prominent phenotypes affecting the lung and hematopoietic system. Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. A large body of new data from Mendelian genetics and epidemiology now provides an opportunity to reconsider paradigms related to the role of telomeres in human aging and cancer, and in some cases, the findings diverge from what was interpreted from model systems. For example, short telomeres have been considered potent drivers of genome instability, but age-associated solid tumors are rare in individuals with short telomere syndromes, and T cell immunodeficiency explains their spectrum. More commonly, short telomeres promote clonal hematopoiesis, including somatic reversion, providing a new leukemogenesis paradigm that is independent of genome instability. Long telomeres, on the other hand, which extend the cellular life span in vitro, are now appreciated to be the most common shared germline risk factor for cancer in population studies. Through this contemporary lens, I revisit here the role of telomeres in human aging, focusing on how short and long telomeres drive cancer evolution but through distinct mechanisms.