Genomic, epigenomic and transcriptomic regulation of cellular senescence

Cellular senescence is a complex, highly regulated cell state induced by cellular damage and stress. Senescence is central to many areas of biology, with roles in tumour suppression, tissue regeneration, antiviral defence and diverse age-related pathologies.\ \n\nRecent technological advances, including new genetic models, single-cell and spatial multi-omics platforms and machine-learning approaches, promise to enable the phenotyping, tracing and manipulation of senescent cells with unprecedented precision and resolution.\ \n\nThis Review defines our current understanding of the genetic pathways that regulate senescence induction, maintenance, propagation and heterogeneity, including the DNA damage response, non-genotoxic stress pathways, epigenetic changes and cell–cell communication.\ \n\nThe authors highlight key challenges in distinguishing senescence from other cell fates and the need for next-generation biomarkers to capture the varied phenotypes and functions of senescent cells.\ \n\nThe complex, dynamic and heterogeneous nature of senescence necessitates a revised mechanistic framework that can accurately capture its regulation and heterogeneity.\ \n\nThis Review provides a comprehensive overview of the current understanding of cellular senescence, highlighting the need for further research and development of novel biomarkers and therapeutic strategies to target senescent cells.