Ageing is a complex biological process in which a gradual decline in physiological fitness increases susceptibility to diseases such as neurodegenerative disorders and cancer. Cellular senescence, a state of irreversible cell-growth arrest accompanied by functional deterioration, has emerged as a pivotal driver of ageing. In this Review, we discuss how heterochromatin loss, telomere attrition and DNA damage contribute to cellular senescence, ageing and age-related diseases by eliciting genome instability, innate immunity and inflammation. We also discuss how emerging therapeutic strategies could restore heterochromatin stability, maintain telomere integrity and boost the DNA repair capacity, and thus counteract cellular senescence and ageing-associated pathologies. Finally, we outline current research challenges and future directions aimed at better comprehending and delaying ageing.

衰老是一个复杂的生物过程，其中生理健康状况的逐渐下降会增加对神经退行性疾病和癌症等疾病的易感性。细胞衰老是一种不可逆的细胞生长停滞伴随着功能退化的状态，已成为衰老的关键驱动因素。在这篇综述中，我们讨论了异染色质丢失、端粒磨损和 DNA 损伤如何通过引发基因组不稳定、先天免疫和炎症来导致细胞衰老、衰老和与年龄相关的疾病。我们还讨论了新兴的治疗策略如何恢复异染色质稳定性、维持端粒完整性并提高 DNA 修复能力，从而抵消细胞衰老和衰老相关病症。最后，我们概述了当前的研究挑战和未来方向，旨在更好地理解和延缓老龄化。