Immunosenescence, aging and successful aging

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 2, 2022

Aging induces a series of immune related changes, which is called immunosenescence, playing important roles in many age-related diseases, especially neurodegenerative tumors, cardiovascular autoimmune diseases and coronavirus disease 2019(COVID-19). However, the mechanism association with aging successful aging, effects on are not revealed obviously. In order to provide theoretical basis for preventing or controlling effectively achieve we conducted review found that changes aging-related phenotypes, deterioration organ function alterations cell subsets participated process had great occurrence development diseases.

Язык: Английский

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Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?

Clinical and Experimental Medicine, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 23, 2025

Cellular senescence is understood to be a biological process that defined as irreversible growth arrest and was originally recognized tumor-suppressive mechanism prevents further propagation of damaged cells. More recently, cellular has been shown have dual role in prevention tumor promotion. Senescent cells carry senescence-associated secretory phenotype (SASP), which altered by factors including pro-inflammatory cytokines, chemokines, other proteases, leading the alteration tissue microenvironment. Though would eventually halt cancerous potential cells, SASP contributes environment promoting inflammation, matrix remodeling, cell invasion. The paradox prevention/promotion particularly relevant bone niche microenvironment, where longer-lasting, chronic inflammation promotes formation. Insights into mechanistic understanding provide basis for targeted therapies, such senolytics, aim eliminate senescent or inhibitors, tumor-promoting effects senescence. These therapeutic interventions offer significant clinical implications treating cancer healthy aging.

Язык: Английский

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The Paradoxical Role of Cellular Senescence in Cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Авг. 12, 2021

Cellular senescence occurs in proliferating cells as a consequence of various triggers including telomere shortening, DNA damage, and inappropriate expression oncogenes. The senescent state is accompanied by failure to reenter the cell cycle under mitotic stimulation, resistance death enhanced secretory phenotype. A growing number studies have convincingly demonstrated paradoxical role for spontaneous therapy-induced (TIS), that may involve both cancer prevention aggressiveness. was initially described physiological suppressor mechanism tumor cells, because development requires proliferation. However, there evidence contribute oncogenesis, partly senescence-associated phenotype (SASP)-dependent manner. On one hand, SASP prevents division promotes immune clearance damaged thereby avoiding development. other contributes progression relapse through creating an immunosuppressive environment. In this review, we performed review summarize bright dark sides cancer, strategies handle therapy were also discussed.

Язык: Английский

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Cellular senescence in cancer: molecular mechanisms and therapeutic targets

MedComm, Год журнала: 2024, Номер 5(5)

Опубликована: Апрель 24, 2024

Abstract Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of senescence on tumor progression has received widespread attention. While how limits course cancer is well established, also been found to promote certain malignant phenotypes. The tumor‐promoting effect mainly elicited by a senescence‐associated secretory phenotype, which facilitates interaction senescent cells their surroundings. Targeting therefore offers promising technique for therapy. Drugs that pharmacologically restore normal function or eliminate them would assist reestablishing homeostasis cell signaling. Here, we describe its occurrence, impact biology. A “one‐two‐punch” therapeutic strategy first induced, followed use senotherapeutics eliminating introduced. advances application targeting treatment are outlined, an emphasis drug categories, strategies screening, design, efficient targeting. This work will foster thorough comprehension encourage additional within this field.

Язык: Английский

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IGFBP5 is released by senescent cells and is internalized by healthy cells, promoting their senescence through interaction with retinoic receptors

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 13, 2024

Abstract Cells that are exposed to harmful genetic damage, either from internal or external sources, may undergo senescence if they unable repair their DNA. Senescence, characterized by a state of irreversible growth arrest, can spread neighboring cells through process known as the senescence-associated secretory phenotype (SASP). This phenomenon contributes both aging and development cancer. The SASP comprises variety factors regulate numerous functions, including induction secondary senescence, modulation immune system activity, remodeling extracellular matrix, alteration tissue structure, promotion cancer progression. Identifying key within is crucial for understanding underlying mechanisms developing effective strategies counteract cellular senescence. Our research has specifically focused on investigating role IGFBP5, component observed in various experimental models conditions. Through our studies, we have demonstrated IGFBP5 actively promoting induce cells. We gained valuable insights into which exerts its pro-senescence effects. These include release following genotoxic stress, involvement signaling pathways mediated reactive oxygen species prostaglandins, internalization via specialized structures called caveolae, interaction with specific protein RARα. By uncovering these mechanisms, advanced intricate process. significance pro-aging factor stems an vivo study conducted patients undergoing Computer Tomography analysis. In patients, elevation circulating levels response radiation-induced organismal stress. Globally, findings highlight potential promising therapeutic target age-related diseases

Язык: Английский

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Macrophages and tumor-associated macrophages in the senescent microenvironment: From immunosuppressive TME to targeted tumor therapy

Pharmacological Research, Год журнала: 2024, Номер 204, С. 107198 - 107198

Опубликована: Апрель 30, 2024

In-depth studies of the tumor microenvironment (TME) have helped to elucidate its cancer-promoting mechanisms and inherent characteristics. Cellular senescence, which acts as a response injury can release senescence-associated secretory phenotypes (SASPs). These SASPs various cytokines, chemokines, growth factors, remodeling TME. This continual development senescent environment could be associated with chronic inflammation immunosuppressive Additionally, influence phenotype function macrophages, leading recruitment tumor-associated macrophages (TAMs). contributes proliferation metastasis in microenvironment, working tandem immune regulation, angiogenesis, therapeutic resistance. comprehensive review covers evolving nature TAMs development. We also explored links between inflammation, TME, cellular macrophages. Moreover, we compiled tumor-specific treatment strategies centered on senescence current challenges research. study aimed clarify mechanism progression advance targeted therapies.

Язык: Английский

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Leveraging Senescent Cancer Cell Membrane to Potentiate Cancer Immunotherapy Through Biomimetic Nanovaccine

Advanced Science, Год журнала: 2024, Номер 11(30)

Опубликована: Июнь 12, 2024

Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cell-based vaccination is limited by interference from immunosuppressive senescence-associated secretory phenotype pro-tumorigenic capacity cells. Here, a nanovaccine strong immunogenicity favorable for immunotherapy reported. The biomimetic integrating cell membrane-coated nanoadjuvant outperforms living in enhancing dendritic (DCs) internalization, improving lymph node targeting, immune responses. In contrast nanovaccines generated death-induced tumor cells, facilitate DC maturation, eliciting superior protection therapeutic outcomes melanoma-challenged mice fewer side effects when combined αPD-1. study suggests versatile biomanufacturing approach maximize minimize adverse advances design immunotherapy.

Язык: Английский

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Polystyrene Nano- and Microplastic Particles Induce an Inflammatory Gene Expression Profile in Rat Neural Stem Cell-Derived Astrocytes In Vitro

Nanomaterials, Год журнала: 2024, Номер 14(5), С. 429 - 429

Опубликована: Фев. 27, 2024

Microplastics are considered an emerging environmental pollutant due to their ubiquitous presence in the environment. However, potential impact of microplastics on human health warrants further research. Recent studies have reported neurobehavioral and neurotoxic effects marine rodent models; however, underlying cellular physiology mammals remains unclear. Herein, we exposed neural stem cells cell-derived astrocytes, oligodendrocytes, neurons various sizes concentrations polystyrene nano- microplastics. We investigated uptake, cytotoxicity, alteration gene expression through transcriptome profiling. The cell type most affected by decreased viability were astrocytes after 7 days repeated exposure. Transcriptional analysis showed that 1274 genes differentially expressed 500 nm microplastics, but only 531 altered 50 nanoplastics. Both canonical pathway Kyoto Encyclopedia Genes Genomes upregulated pathways involved neuroinflammation, innate adaptive immunity, migration, proliferation, extracellular matrix remodeling, cytoskeleton structures. downregulated lipid metabolism, specifically fatty acid oxidation cholesterol metabolism. Our results show repeatedly for undergo changes hallmarks astrogliosis.

Язык: Английский

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A stumbling block in pancreatic cancer treatment: drug resistance signaling networks

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Янв. 13, 2025

The primary node molecules in the cell signaling network cancer tissues are maladjusted and mutated comparison to normal tissues, which promotes occurrence progression of cancer. Pancreatic (PC) is a highly fatal with increasing incidence low five-year survival rates. Currently, there several therapies that target networks PC. However, PC "cold tumor" unique immunosuppressive tumor microenvironment (poor effector T infiltration, antigen specificity), targeting single gene or pathway basically ineffective clinical practice. Targeted matrix therapy, targeted metabolic mutant vaccines, other emerging have shown great therapeutic potential, but results been disappointing. Therefore, we summarize identified potential drug-resistant aimed at overcoming barriers existing therapies.

Язык: Английский

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Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer

Frontiers in Cardiovascular Medicine, Год журнала: 2021, Номер 8

Опубликована: Окт. 20, 2021

Overlapping risks for cancer and cardiovascular diseases (CVD), the two leading causes of mortality worldwide, suggest a shared biology between these diseases. The role senescence in development CVD has been established. However, its as intersection remains unclear. Senescence was originally characterized by an irreversible cell cycle arrest after high number divisions, namely replicative (RS). it is becoming clear that can also be instigated cellular stress, so-called stress-induced premature (SIPS). Telomere shortening hallmark RS. contribution telomere DNA damage subsequent response/repair to SIPS suggested. Although mediate arrest, senescent cells remain metabolically active secrete cytokines, chemokines, growth factors, reactive oxygen species (ROS), senescence-associated secretory phenotype (SASP). involvement SASP both In patients with or CVD, induced various stressors including treatments, pro-inflammatory ROS. Therefore, CVD. Importantly, conventional concept mediator challenged, recently reported chemotherapy-induced reprogram acquire “stemness” (SAS: stemness). SAS allows escape strongly enhanced clonogenic capacity. supports promote particularly highly stressful conditions such myocardial infarction, heart failure. As therapeutic advances have increased overlapping risk factors further understand their interaction may provide better prevention, earlier detection, safer treatment. Thus, critical study mechanisms which pathways (SAS/SASP) are regulated

Язык: Английский

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