Guidelines for minimal information on cellular senescence experimentation in vivo

Cell, Год журнала: 2024, Номер 187(16), С. 4150 - 4175

Опубликована: Авг. 1, 2024

Cellular senescence is a cell fate triggered in response to stress and characterized by stable cell-cycle arrest hypersecretory state. It has diverse biological roles, ranging from tissue repair chronic disease. The development of new tools study vivo paved the way for uncovering its physiological pathological roles testing senescent cells as therapeutic target. However, lack specific broadly applicable markers makes it difficult identify characterize tissues living organisms. To address this, we provide practical guidelines called "minimum information cellular experimentation vivo" (MICSE). presents an overview rodent tissues, transgenic models, non-mammalian systems, human tumors their use identification specification cells. These uniform, state-of-the-art, accessible toolset improve our understanding vivo.

Язык: Английский

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Cellular senescence: Neither irreversible nor reversible

The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(4)

Опубликована: Фев. 22, 2024

Cellular senescence is a critical stress response program implicated in embryonic development, wound healing, aging, and immunity, it backs up apoptosis as an ultimate cell-cycle exit mechanism. In analogy to replicative exhaustion of telomere-eroded cells, premature types senescence—referring oncogene-, therapy-, or virus-induced senescence—are widely considered irreversible growth arrest states well. We discuss here that entry into full-featured not necessarily permanent endpoint, but dependent on essential maintenance components, potentially transient. Unlike binary state switch, we view with its extensive epigenomic reorganization, profound cytomorphological remodeling, distinctive metabolic rewiring rather journey toward condition variable strength depth. Senescence-underlying maintenance-essential molecular mechanisms may allow reentry if continuously provided. Importantly, senescent cells resumed proliferation fundamentally differ from those never entered senescence, hence would reflect reversion dynamic progression post-senescent comes distinct functional clinically relevant ramifications.

Язык: Английский

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The Common Hallmarks of Aging, Circadian Rhythms and Cancer: Implications for Therapeutic Strategies

Research, Год журнала: 2025, Номер 8

Опубликована: Янв. 1, 2025

The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis cancer progression. Aging well-established primary risk for while disruptions rhythms are intricately associated with progression of various tumors. Moreover, itself disrupts leading to physiological changes that may accelerate development. Despite these connections, specific interplay processes their collective impact on remains inadequately explored literature. In this review, we systematically explore influence We discuss how core genes tumor prognosis, highlighting shared hallmarks such genomic instability, cellular senescence, chronic inflammation. Furthermore, examine aging, focusing crosstalk contributes tumorigenesis, proliferation, apoptosis, well metabolism stability. By elucidating common pathways linking review provides new insights into pathophysiology identifies potential therapeutic strategies. propose targeting regulation could pave way novel treatments, including chronotherapy antiaging interventions, which offer important benefits clinical management cancer.

Язык: Английский

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Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 2, 2025

Cellular senescence, a stable state of cell cycle arrest induced by various stressors or genomic damage, is recognized as hallmark cancer. It exerts context-dependent dual role in cancer initiation and progression, functioning tumor suppressor promoter. The complexity senescence arises from its mechanistic diversity, potential reversibility, heterogeneity. A key mediator these effects the senescence-associated secretory phenotype (SASP), repertoire bioactive molecules that influence microenvironment (TME) remodeling, modulate behavior, contribute to therapeutic resistance. Given intricate biology, presents both challenges opportunities for intervention. Strategies targeting pathways, including senescence-inducing therapies senolytic approaches, offer promising avenues treatment. This review provides comprehensive analysis regulatory mechanisms governing cellular tumors. We also discuss emerging strategies highlighting novel opportunities. deeper understanding processes essential developing precision improving clinical outcomes.

Язык: Английский

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Subcellular structure, heterogeneity, and plasticity of senescent cells

Aging Cell, Год журнала: 2024, Номер 23(4)

Опубликована: Март 30, 2024

Abstract Cellular senescence is a state of permanent growth arrest. It can be triggered by telomere shortening (replicative senescence) or prematurely induced stresses such as DNA damage, oncogene overactivation, loss tumor suppressor genes, oxidative stress, tissue factors, and others. Advances in techniques experimental designs have provided new evidence about the biology senescent cells (SnCs) their importance human health disease. This review aims to describe main aspects SnCs phenotype focusing on alterations subcellular compartments like plasma membrane, cytoskeleton, organelles, nuclei. We also discuss heterogeneity, dynamics, plasticity SnCs' phenotype, including SASP, pro‐survival mechanisms. advance multiple layers phenotypic heterogeneity SnCs, between inducers, tissues within population discussing relevance these raise challenges well alternatives overcome them. Ultimately, we present open questions perspectives understanding from perspective basic applied questions.

Язык: Английский

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Loss of the tumour suppressor LKB1/STK11 uncovers a leptin-mediated sensitivity mechanism to mitochondrial uncouplers for targeted cancer therapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июль 25, 2024

Abstract Non-small cell lung cancer (NSCLC) constitutes one of the deadliest and most common malignancies. The LKB1/STK11 tumour suppressor is mutated in ∼ 30% NSCLCs, typically adenocarcinomas (LUAD). We implemented zebrafish human organoids as synergistic platforms to pre-clinically screen for metabolic compounds selectively targeting LKB1-deficient tumours. Interestingly, two kinase inhibitors, Piceatannol Tyrphostin 23, appeared exert synthetic lethality with LKB1 mutations. Although loss alone accelerates energy expenditure, unexpectedly we find that it additionally alters regulation key homeostasis maintenance player leptin (LEP), further increasing energetic burden exposing a vulnerable point; acquired sensitivity identified compounds. show compound treatment stabilises Hypoxia-inducible factor 1-alpha (HIF1A) by antagonising Von Hippel-Lindau (VHL)-mediated HIF1A ubiquitination, driving LEP hyperactivation. Importantly, demonstrate piceatannol/tyrphostin 23 epistatically relies on HIF1A-LEP-Uncoupling Protein 2 (UCP2) signaling axis lowering cellular beyond survival, already challenged cells. Thus, uncover pivotal vulnerability tumours, which may be therapeutically exploited using our mitochondrial uncouplers.

Язык: Английский

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Therapy-Induced Cellular Senescence: Potentiating Tumor Elimination or Driving Cancer Resistance and Recurrence?

Cells, Год журнала: 2024, Номер 13(15), С. 1281 - 1281

Опубликована: Июль 30, 2024

Cellular senescence has been increasingly recognized as a hallmark of cancer, reflecting its association with aging and inflammation, role response to deregulated proliferation oncogenic stress, induction by cancer therapies. While therapy-induced (TIS) linked resistance, recurrence, metastasis, normal tissue toxicity, TIS also the potential enhance therapy stimulate anti-tumor immunity. In this review, we examine Jekyll Hyde nature senescent cells (SnCs), focusing on how their persistence while expressing senescence-associated secretory phenotype (SASP) modulates tumor microenvironment through autocrine paracrine mechanisms. Through SASP, SnCs can mediate both resistance To fulfill unmet immunotherapy, consider may influence inflammation serve an antigen source potentiate immune response. This new perspective suggests treatment approaches based checkpoint blockade. Finally, describe strategies for mitigating detrimental effects senescence, such modulating SASP or targeting SnC persistence, which overall benefits treatment.

Язык: Английский

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Current Methodologies to Assess Cellular Senescence in Cancer

Methods in molecular biology, Год журнала: 2025, Номер unknown, С. 21 - 44

Опубликована: Янв. 1, 2025

Язык: Английский

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Pulsed Electromagnetic Fields (PEMFs) Trigger Cell Death and Senescence in Cancer Cells

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2473 - 2473

Опубликована: Фев. 20, 2024

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death cellular senescence not only in cancer cells but also the adjacent normal tissue. New anti-tumor approaches focus on limiting side effects cells. In this frame, potential properties of Pulsed Electromagnetic Fields (PEMFs) through irradiation breast epithelial (MCF-7 MDA-MB-231) fibroblasts (FF95) were investigated. PEMFs had a frequency 8 Hz, full-square wave type magnetic flux density 0.011 T applied twice daily for 5 days. data collected showcase that PEMF application decreases proliferation rate viability while having opposite effect fibroblasts. Moreover, induces without any non-cancerous These findings suggest novel, non-invasive strategy that, when combined with senolytic drugs, may eliminate both remaining senescent cells, simultaneously avoiding current treatments.

Язык: Английский

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One-step rapid tracking and isolation of senescent cells in cellular systems, tissues, or animal models via GLF16

STAR Protocols, Год журнала: 2024, Номер 5(1), С. 102929 - 102929

Опубликована: Март 1, 2024

Identification and isolation of senescent cells is challenging, rendering their detailed analysis an unmet need. We describe a precise one-step protocol to fluorescently label cells, for flow cytometry fluorescence microscopy, implementing fluorophore-conjugated Sudan Black-B analog, GLF16. Also, micelle-based approach allows identification in vivo vitro, enabling live-cell sorting downstream analyses live tracking. Our protocols are applicable cellular systems, tissues, or animal models where senescence present. For complete details on the use execution this protocol, please refer Magkouta et al.1

Язык: Английский

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