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Cellular senescence is a state of durable cell arrest that has been identified both in vitro and in vivo. It is associated with profound changes in gene expression and a specific secretory profile that includes pro‐inflammatory cytokines, growth factors and matrix‐remodelling enzymes, referred to as the senescence‐associated secretory phenotype (SASP). In cancer, senescence can have anti‐ or pro‐tumour effects. On one hand, it can inhibit tumour progression in a cell autonomous manner. On the other hand, senescence can also promote tumour initiation, progression, metastatic dissemination and resistance to therapy in a paracrine manner. Therefore, despite efforts to target senescence as a potential strategy to inhibit tumour growth, senescent cancer and microenvironmental cells can eventually lead to uncontrolled proliferation and aggressive tumour phenotypes. This can happen either through overcoming senescence growth arrest or through SASP‐mediated effects in adjacent tumour cells. This review will discuss how senescence affects the tumour microenvironment, including extracellular matrix remodelling, the immune system and the vascular compartment, to promote tumourigenesis, metastasis and resistance to DNA‐damaging therapies. It will also discuss current approaches used in the field to target senescence: senolytics, improving the immune clearance of senescent cells and targeting the SASP. [ABSTRACT FROM AUTHOR]

The contribution of cellular senescence to a diverse range of biological processes, including normal physiology, ageing, and pathology were long overlooked but have now taken centre stage. In this Editorial, we will briefly outline the review and original work articles contained in The FEBS Journal's Special Issue on Senescence in Ageing and Disease. It is beginning to be appreciated that senescent cells can exert both beneficial and adverse effects following tissue injury. Additionally, while these cells play critical roles for maintaining a healthy physiology, they also promote ageing and certain pathological conditions (including developmental disorders). Progress has been made in re‐defining and identifying senescent cells, especially in slow‐proliferating or terminally differentiated tissues, such as the brain and cardiovascular system. Novel approaches and techniques for isolating senescent cells will greatly increase our appreciation for senescent properties in tissues. The inter‐organ communication between senescent cells and other residents of the tissue microenvironment, via the senescence‐associated secretory phenotype (SASP), is a focus of several reviews in this Special Issue. The importance of the SASP in promoting tumour development and the evolution of SARS CoV‐2 variants is also highlighted. In one of the two original articles included in the issue, the impact of dietary macronutrients and the presence of senescent cells in mice is investigated. Lastly, we continue to deepen our understanding on the use of senolytics and senomorphics to specifically target senescent cells or their secreted components, respectively, which is discussed in several of the reviews included here. [ABSTRACT FROM AUTHOR]

Cellular senescence is a distinct state that is frequently induced in response to ageing and stress. Yet studies have also uncovered beneficial functions in development, repair and regeneration. Current opinion therefore suggests that timely and controlled induction of senescence can be beneficial, while misregulation of the senescence program, either through mis‐timed activation, or chronic accumulation of senescent cells, contributes to many disease states and the ageing process. Whether atypical activation of senescence plays a role in the pathogenesis of developmental defects has been relatively underexplored. Here, we discuss three recent studies that implicate ectopic senescence in neurodevelopmental defects, with possible causative roles for senescence in these birth defects. In addition, we highlight how the examination of senescence in other birth defects is warranted, and speculate that aberrantly activated senescence may play a much broader role in developmental defects than currently appreciated. [ABSTRACT FROM AUTHOR]

Cellular senescence refers to a state of irreversible cell cycle arrest that can be induced by various cellular stresses and is known to play a pivotal role in tumour suppression. While senescence‐associated growth arrest can inhibit the proliferation of cancer‐prone cells, the altered secretory profile of senescent cells, termed the senescence‐associated secretory phenotype, can contribute to the microenvironment that promotes tumour development. Although the senescence‐associated secretory phenotype and its effects on tumorigenesis are both highly context dependent, mechanisms underlying such diversity are becoming better understood, thereby allowing the creation of new strategies to effectively target the senescence‐associated secretory phenotype and senescent cells for cancer therapy. In this review, we discuss the current knowledge on cellular senescence and the senescence‐associated secretory phenotype to develop a structural understanding of their roles in the tumour microenvironment and provide perspectives for future research, including the possibility of senotherapy for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Cellular senescence is a process in which cells change their characteristic phenotype in response to stress and enter a state of prolonged cell cycle arrest accompanied by a distinct secretory phenotype. Cellular senescence has both beneficial and detrimental outcomes. With age, senescent cells progressively accumulate in tissues and might be the bridge connecting ageing to many age‐related pathologies. In recent years, evidence emerged supporting the accumulation of brain senescent cells during neurological disorders and ageing. Here, we will discuss the different brain cell populations that exhibit a senescent phenotype. Subsequently, we will explore several senolytic strategies which have been developed to eliminate senescent cells. Finally, we will examine their potential to directly eliminate these senescent brain cells. [ABSTRACT FROM AUTHOR]

Cellular senescence within the cardiovascular system has, until recently, been understudied and unappreciated as a factor in the development of age‐related cardiovascular diseases such as heart failure, myocardial infarction and atherosclerosis. This is in part due to challenges with defining senescence within post‐mitotic cells such as cardiomyocytes. However, recent evidence has demonstrated senescent‐like changes, including a senescence‐associated secretory phenotype (SASP), in cardiomyocytes in response to ageing and cell stress. Other replicating cells, including fibroblasts and vascular smooth muscle cells, within the cardiovascular system have also been shown to undergo senescence and contribute to disease pathogenesis. These findings coupled with the emergence of senolytic therapies, to target and eliminate senescent cells, have provided fascinating new avenues for management of several age‐related cardiovascular diseases with high prevalence. In this review, we discuss the role of senescent cells within the cardiovascular system and highlight the contribution of senescence cells to common cardiovascular diseases. We discuss the emerging role for senolytics in cardiovascular disease management while highlighting important aspects of senescence biology which must be clarified before the potential of senolytics can be fully realized. [ABSTRACT FROM AUTHOR]

The concept of geroscience is that since ageing is the greatest risk factor for many diseases and conditions, targeting the ageing process itself will have the greatest impact on human health. Of the hallmarks of ageing, cellular senescence has emerged as a druggable therapeutic target for extending healthspan in model organisms. Cellular senescence is a cell state of irreversible proliferative arrest driven by different types of stress, including oncogene‐induced stress. Many senescent cells (SnCs) develop a senescent‐associated secretory phenotype (SASP) comprising pro‐inflammatory cytokines, chemokines, proteases, bioactive lipids, inhibitory molecules, extracellular vesicles, metabolites, lipids and other factors, able to promote chronic inflammation and tissue dysfunction. SnCs up‐regulate senescent cell anti‐apoptotic pathways (SCAPs) that prevent them from dying despite the accumulation of damage to DNA and other organelles. These SCAPs and other pathways altered in SnCs represent therapeutic targets for the development of senotherapeutic drugs that induce selective cell death of SnCs, specifically termed senolytics or suppress markers of senescence, in particular the SASP, termed senomorphics. Here, we review the current state of the development of senolytics and senomorphics for the treatment of age‐related diseases and disorders and extension of healthy longevity. In addition, the challenges of documenting senolytic and senomorphic activity in pre‐clinical models and the current state of the clinical application of the different senotherapeutics will be discussed. [ABSTRACT FROM AUTHOR]

Cellular senescence is an irreversible cell cycle arrest caused by various stressors that damage cells. Over time, senescent cells accumulate and contribute to the progression of multiple age-related degenerative diseases. It is believed that these cells accumulate partly due to their ability to evade programmed cell death through the development and activation of survival and antiapoptotic resistance mechanisms; however, many aspects of how these survival mechanisms develop and activate are still unknown. By analyzing transcriptomic signature profiles generated by the LINCS L1000 project and using network-based methods, we identified various genes that could represent new senescence-related survival mechanisms. Additionally, employing the same methodology, we identified over 600 molecules with potential senolytic activity. Experimental validation of our computational findings confirmed the senolytic activity of Fluorouracil, whose activity would be mediated by a multitarget mechanism, revealing that its targets AURKA, EGFR, IRS1, SMAD4, and KRAS are new senescent cell antiapoptotic pathways (SCAPs). The development of these pathways could depend on the stimulus that induces cellular senescence. The SCAP development and activation mechanisms proposed in this work offer new insights into how senescent cells survive. Identifying new antiapoptotic resistance targets and drugs with potential senolytic activity paves the way for developing new pharmacological therapies to eliminate senescent cells selectively., (© 2025 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Senescent cells accumulate with aging and at etiological sites of multiple diseases, including those accounting for most morbidity, mortality, and health costs. Senescent cells do not replicate, can release factors that cause tissue dysfunction, and yet remain viable. The discovery of senolytic drugs, agents that selectively eliminate senescent cells, created a new route for alleviating age‐related dysfunction and diseases. As anticipated for agents targeting fundamental aging mechanisms that are 'root cause' contributors to multiple disorders, potential applications of senolytics are protean. We review the discovery of senolytics, strategies for translation into clinical application, and promising early signals from clinical trials. [ABSTRACT FROM AUTHOR]