Genomic, epigenomic and transcriptomic regulation of cellular senescence.

Cellular senescence is a highly regulated stress-induced cell state marked by stable cell-cycle arrest, chromatin remodeling, metabolic changes, and a senescence-associated secretory phenotype.

• Why it matters: Understanding how senescence is induced, maintained, and diversified is crucial because it underpins tumor suppression, tissue regeneration, antiviral defense, and multiple age-related pathologies.
• What they did: This Review synthesizes current knowledge of genetic pathways controlling senescence induction, maintenance, propagation, and heterogeneity, covering DNA damage response, non-genotoxic stress, epigenetic changes, and cell-cell communication.
• The result: It highlights challenges in distinguishing senescence from other cell fates and argues that next-generation biomarkers are needed to capture varied senescent phenotypes and functions.

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