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Cell senescence — a state of irreversible cell-growth arrest — has important physiological functions and is a key driver of ageing. The articles in this Focus explore the molecular mechanisms that induce cell senescence, functional consequences for surrounding tissues, emerging therapies to counteract senescent-associated diseases, and recommendations for identifying senescent cells.
The senescence-associated secretory phenotype (SASP) mediates the tissue effects of senescent cells. This Review discusses the composition, regulation and various biological implications of the SASP and its uses as a biomarker and a target of senomorphic drugs to treat cancer and other age-related conditions.
Heterochromatin loss, telomere attrition and DNA damage induce cellular senescence by eliciting genome instability and innate immunity responses, thereby promoting ageing and age-related diseases. This Review discusses the underlying mechanisms of these processes and emerging cell-senescence therapeutics that target them.
Senescent cells have complex and important roles in cancer and ageing, but they are quite rare and difficult to characterize in tissues in vivo. In this Expert Recommendation, the SenNet Biomarkers Working Group discusses recent advances in detecting and characterizing cellular senescence and provides recommendations for senescence markers in 14 human and mouse tissues.
In this Tools of the Trade article, Duran (Gil lab) describes the development of novel machine learning algorithms that enable the detection of senescent cells in vitro and in diverse tissues based solely on nuclear morphologeny analysis.
In the Journal Club, Fabrizio d’Adda di Fagagna remembers how the work of Judy Campisi changed our understanding of cellular senescence and its effect on physiology and ageing, shaping the future of this research field.
Akiko Takahashi discusses the seminal 1997 paper by Serrano et al. who found that oncogene activation results in a similar phenotype to replicative senescence, establishing the connection between senescence and cancer.
Senescent cells in the amputated head of the cnidarian Hydractinia symbiolongicarpus drive the reprogramming of somatic cells into pluripotent stem cells, which are required for full body regeneration.
James Kirkland discusses how work by Norman Sharpless and colleagues, published in 2004, paved the way for the development of senolytics, which are now in early phase clinical trials for the treatment of multiple disorders.
Enrichment of senescent cells from organs holds great promise for studying cell senescence and ageing, and for identifying therapeutic vulnerabilities.
Ana O’Loghlen highlights a recent study that indicates that inhibiting the pro-inflammatory cytokine IL-11 has anti-ageing effects, and how such findings could have implications for the treatment of ageing-associated diseases.