Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions

Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102315 - 102315

Опубликована: Апрель 26, 2024

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two types exist where non-small cell lung (NSCLC), accounts for 80–85% and SCLC 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous carcinoma, large carcinoma. Smoking, second-hand smoke, radon gas, asbestos, other pollutants, genetic predisposition, COPD are risk factors. On hand, stresses such DNA damage, telomere shortening, oncogene activation cause a prolonged cycle halt, known senescence. Despite its initial role tumor-suppressing mechanism that slows growth, excessive or improper control this process can age-related diseases, including cancer. Cellular senescence has two purposes in Researchers report tumor growth by constraining multiplication impaired cells. However, senescent cells also demonstrate pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported promote This review will look at cellular cancer, describe diagnostic markers, ask about current treatments it, case studies clinical trials show how senescence-targeting therapies be used talk problems currently being faced, possible solutions same future.

Язык: Английский

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Focus on senescence: Clinical significance and practical applications

Journal of Internal Medicine, Год журнала: 2024, Номер 295(5), С. 599 - 619

Опубликована: Март 6, 2024

Abstract The older population is increasing worldwide, and life expectancy continuously rising, predominantly thanks to medical technological progress. Healthspan refers the number of years an individual can live in good health. From a gerontological viewpoint, mission extend spent health, promoting well‐being minimizing impact aging‐related diseases slow aging process. Biologically, malleable process characterized by intra‐ inter‐individual heterogeneous dynamic balance between accumulating damage repair mechanisms. Cellular senescence key component this process, with senescent cells different tissues organs, leading age‐related disease susceptibility over time. Removing from body or slowing down burden rate has been proposed as efficient way reduce age‐dependent deterioration. In animal models, senotherapeutic molecules lifespan either senolytic senomorphic activity. Much research shows that dietary physical activity‐driven lifestyle interventions protect against senescence. This narrative review aims summarize current knowledge on targeting risk models their translational potential for humans. We focused studies have examined role senotherapeutics modifying burdens. concludes general discussion mechanisms underlying unique trajectory its implications future research.

Язык: Английский

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Mechanisms and Strategies of Immunosenescence Effects on Non-Small Cell Lung Cancer (NSCLC) Treatment: A Comprehensive Analysis and Future Directions

Seminars in Cancer Biology, Год журнала: 2025, Номер 109, С. 44 - 66

Опубликована: Янв. 9, 2025

Язык: Английский

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Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants

Aging and Disease, Год журнала: 2024, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2024

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling determinants of fate. Beginning with an overview aging's significance in explores processes, changes, molecular pathways influencing senescence. The senescence as a dual mechanism acting suppressor contributor, focusing on its impact therapy response. highlights opportunities for cancer therapies that target further examines senescence-associated secretory phenotype strategies to modulate aging influence tumor behavior. Additionally, mechanisms escape cells, emphasizing their prognosis resistance therapy. article addresses current advances, unexplored aspects, future perspectives understanding cancer.

Язык: Английский

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From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications

Biomolecules, Год журнала: 2025, Номер 15(3), С. 327 - 327

Опубликована: Фев. 24, 2025

Lysosomes are essential intracellular organelles involved in plentiful cellular processes such as cell signaling, metabolism, growth, apoptosis, autophagy, protein processing, and maintaining homeostasis. Their dysfunction is linked to various diseases, including lysosomal storage disorders, inflammation, cancer, cardiovascular neurodegenerative conditions, aging. This review focuses on current emerging therapies for diseases (LDs), small medicines, enzyme replacement therapy (ERT), gene therapy, transplantation, drug targeting (LDT). study was conducted through databases like PubMed, Google Scholar, Science Direct, other research engines. To treat LDs, medicines target the membrane, acidification processes, cathepsins, calcium mTOR, autophagy. Moreover, small-molecule using chaperones, macro-therapies ERT, editing technologies used LDs. Additionally, endosymbiotic artificial lysosomes, transplantation promising options LD management. LDT enhances therapeutic outcomes Extracellular vesicles mannose-6-phosphate-tagged nanocarriers display approaches improving LDT. concluded that lysosomes play a crucial role pathophysiology of numerous diseases. Thus, restoring function treating wide range conditions. Despite offering significant potential control, there ample challenges regarding safety ethical implications.

Язык: Английский

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Targeting senescence in Amyotrophic Lateral Sclerosis: senolytic treatment improves neuromuscular function and preserves cortical excitability in a TDP-43Q331K mouse model.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary cortex (PMC) and spinal cord. Aging key factor ALS onset progression, with evidence suggesting that biological aging-a process involving cellular decline- far outpaces chronological aging ALS. This promotes senescent cell accumulation-marked irreversible cell-cycle arrest, impaired apoptosis, chronic inflammation-disrupting tissue homeostasis impairing neuronal support functions. Thus, targeting senescence presents novel therapeutic strategy for Here, we investigated senolytic combination Dasatinib Quercetin (D&Q) TDP-43 Q331K mice. D&Q improved neuromuscular function reduced plasma neurofilament light chain, biomarker of axonal damage. The most pronounced improvement was cortical excitability, accompanied reductions PMC. These findings highlight potential senolytics to mitigate ALS-related dysfunction, supporting their viability as strategy. *Jose A. Viteriab, Nathan R. Kerrab, Charles D. Brennana are co-first authors.

Язык: Английский

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Human dermal fibroblast senescence in response to single and recurring oxidative stress

Frontiers in Aging, Год журнала: 2025, Номер 6

Опубликована: Март 28, 2025

Introduction: Aging results in an accumulation of damaged cells, which reduces the health tissues and their regenerative capabilities. In skin, there are both internal external drivers oxidative stress that result aging phenotypes. Oxidative has been used to model senescence vitro; however, a lack research determining whether severity correlates with senescent Methods: this work, we compare cellular secretory responses single (500 μM hydrogen peroxide, 2 hours) or recurring dose peroxide hours + 4 × 300 each 48 hours). Senescence induction was studied using markers including cell morphology, senescence-associated-beta-galactosidase, absence apoptosis, cycle inhibition genes. Next, functional studies effects signaling these cells were completed, such as vascular potential, keratinocyte proliferation, macrophage polarization. Results: Fibroblasts exposed had increased total nucleic area, senescence-associated-beta-galactosidase (SABGAL) expression, they able escape apoptosis - all characteristics cells. Additionally, expressed levels inhibitor genes decreased expression collagen-I, -III, -IV. Cytokine profiling showed stressed more inflammatory profile. However, assays, reduced IL-1β gene unpolarized polarized macrophages. Discussion: The described protocol allows for investigation direct fibroblasts on surrounding healthy These show recurringly represent intense phenotype, can be vitro understand responses.

Язык: Английский

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Network pharmacology and molecular docking approach to elucidate potential phytocompounds, targets, and mechanisms of Glycyrrhiza glabra in the alleviation of cellular senescence

Phytomedicine Plus, Год журнала: 2024, Номер 4(3), С. 100579 - 100579

Опубликована: Май 17, 2024

There is an increasing interest in identifying modulators of cellular senescence as potential anti-ageing agents. Nutritional modulation pragmatic and medicinal plants are attractive sources anti-cellular drug candidates. Glycyrrhiza glabra (GG) extensively utilized plant its effects also known. The current study attempted to understand the targets GG components their underlying pathways using network pharmacology validation through silico molecular docking. Components were screened Dr. Duke's Phytochemical Ethnobotanical Database KNApSAcK database, target prediction was done SuperPred 3.0, followed by mapping with gene obtained from GeneCards CellAge databases. STRING database Cytoscape software for protein-protein protein-target interaction analyses further screening core targets. GO KEGG enrichment analysis performed, top identified subject binding affinity evaluation major compounds 40 overlapped 71 senescence. PPI revealed HIF1A, HSP90AB1, NF-κB1, STAT1, HDAC2 while showed protein phosphorylation folding be targeted biological processes. 'pathways cancer' 'MAPK signalling pathway' enriched several classical regulators that GG. 4'-O-methylglabridin glycyrrhisoflavanone categorically appeared most potent interacting average < 7.0 kcal/mol. Molecular docking very strong affinities (< kcal/mol) CDK2, NFE2L2, HIF1A. Together, our research paves way subsequent experimental verification novel could useful developing GG-based herbal approaches.

Язык: Английский

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Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach

Aging and Disease, Год журнала: 2024, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2024

Diabetic foot ulcers (DFUs) are a prevalent and profoundly debilitating complication that afflicts individuals with diabetes mellitus (DM). These associated substantial morbidity, recurrence rates, disability, mortality, imposing economic, psychological, medical burdens. Timely detection intervention can mitigate the morbidity disparities linked to DFU. Nevertheless, current therapeutic approaches for DFU continue grapple multifaceted limitations. A growing body of evidence emphasizes crucial role cellular senescence in pathogenesis chronic wounds. Interventions try delay senescence, eliminate senescent cells (SnCs), or suppress senescence-associated secretory phenotype (SASP) have shown promise helping wounds heal. In this context, targeting emerges as novel strategy comprehensive review, we look at pathology treatment systematic way. We also explain importance investigating SnCs highlight great potential senotherapeutics target treatment. The development efficacious safe represents pioneering approach aimed enhancing quality life affected by

Язык: Английский

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Senescent cell-derived vaccines: a new concept towards an immune response against cancer and aging?

Aging, Год журнала: 2024, Номер 16(12), С. 10657 - 10665

Опубликована: Июнь 26, 2024

Two recent seminal works have untangled the intricate role of tumor-associated senescent cells in cancer progression, or regression, by guiding our immune system against cells. The characterization these unique, yet diverse cell populations, should be considered, particularly when contemplating use senolytics, which are drugs that selectively eliminate cells, a framework. Here, we will describe current knowledge this field. In particular, discuss how presence tumors could used as therapeutic target immunogenic cancers and may hypothetically design an adaptive anti-aging vaccine.

Язык: Английский

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