Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Nat Rev Mol Cell Biol. 2024 Dec;25(12):979-1000. doi: 10.1038/s41580-024-00775-3. Epub 2024 Oct 3.
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学过程，在此过程中，生理功能逐渐衰退，导致易患神经退行性疾病和癌症等疾病。细胞衰老，即不可逆的细胞生长停滞并伴有功能恶化的状态，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性、先天免疫和炎症，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、维持端粒完整性和增强 DNA 修复能力，从而抵抗细胞衰老和与衰老相关的病理。最后，我们概述了当前旨在更好地理解和延缓衰老的研究挑战和未来方向。
