Aging of the cells: Insight into cellular senescence and detection Methods

European Journal of Cell Biology, Год журнала: 2020, Номер 99(6), С. 151108 - 151108

Опубликована: Июль 12, 2020

Язык: Английский

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The Cytoskeleton as Regulator of Cell Signaling Pathways

Trends in Biochemical Sciences, Год журнала: 2019, Номер 45(2), С. 96 - 107

Опубликована: Дек. 5, 2019

Язык: Английский

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The lysosomal proteome of senescent cells contributes to the senescence secretome

Aging Cell, Год журнала: 2022, Номер 21(10)

Опубликована: Сен. 10, 2022

Abstract Senescent cells accumulate in tissues over time, favoring the onset and progression of multiple age‐related diseases. present a remarkable increase lysosomal mass elevated autophagic activity. Here, we report that two main pathways macroautophagy (MA) chaperone‐mediated autophagy (CMA) are constitutively upregulated senescent cells. Proteomic analyses subpopulations lysosomes preferentially engaged each these types revealed profound quantitative qualitative changes cells, affecting both resident proteins cargo delivered to for degradation. These studies have led us identify highly augmented can be used as novel markers senescence, such arylsulfatase ARSA. The abundant secretome known SASP, is considered their pathological mediator; however, little about mechanisms SASP secretion. Some secretory including melanocytes, use small GTPase RAB27A perform We found this process exacerbated case melanoma by exposure membrane integral LAMP1 LAMP2 plasma membrane. Interestingly, subset components, cytokines CCL2, CCL3, CXCL12, cathepsin CTSD, or protease inhibitor SERPINE1, secreted RAB27A‐dependent manner Finally, previously identified biomarkers aging enriched CTSD. conclude proteome profoundly reconfigured, some active exocytosis.

Язык: Английский

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Hallmarks and Biomarkers of Skin Senescence: An Updated Review of Skin Senotherapeutics

Antioxidants, Год журнала: 2023, Номер 12(2), С. 444 - 444

Опубликована: Фев. 10, 2023

Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and increased probability of death. Cellular senescence has been typically considered as anti-proliferative process; however, the chronic accumulation senescent cells contributes tissue dysfunction aging. In this review, we discuss some most important hallmarks biomarkers cellular with special focus on skin biomarkers, reactive oxygen species (ROS), senotherapeutic strategies eliminate or prevent senescence. Although them are not exclusive senescence, expression senescence-associated beta-galactosidase (SA-β-gal) enzyme seems be reliable biomarker for distinguishing from those arrested cell cycle. The presence stable DNA damage response (DDR) secretory phenotype (SASP) mediators ROS representative Senotherapeutics based natural compounds such quercetin, naringenin, apigenin have shown promising results regarding SASP reduction. These seem cells, likely through inhibition pro-survival signaling pathways. studies still required verify their short- long-term effects, these therapies may effective strategy

Язык: Английский

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Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions

Aging, Год журнала: 2024, Номер 16(4), С. 3088 - 3106

Опубликована: Фев. 22, 2024

Aging | doi:10.18632/aging.205581. Edwin Lee, Natàlia Carreras-Gallo, Leilani Lopez, Logan Turner, Aaron Lin, Tavis L. Mendez, Hannah Went, Alan Tomusiak, Eric Verdin, Michael Corley, Lishomwa Ndhlovu, Ryan Smith, Varun B. Dwaraka

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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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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Emerging role of microtubule-associated proteins on cancer metastasis

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Сен. 14, 2022

The major cause of death in cancer patients is strongly associated with metastasis. While much remains to be understood, microtubule-associated proteins (MAPs) have shed light on metastatic progression’s molecular mechanisms. In this review article, we focus the role MAPs aggressiveness, particularly metastasis activity. Increasing evidence has shown that a growing number MAP member might fundamental regulators involved altering microtubule dynamics, contributing migration, invasion, and epithelial-to-mesenchymal transition. types been established according their microtubule-binding site function microtubule-dependent activities. We highlight altered expression was commonly found many related progression based available evidence. Furthermore, discuss integrate relevance signaling pathways Our provides comprehensive understanding microtubules. It elucidates how regulate progression, preferentially metastasis, providing substantial scientific information as potential therapeutic targets prognostic markers for management.

Язык: Английский

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Characterizing microglial senescence: Tau as a key player

Journal of Neurochemistry, Год журнала: 2023, Номер 166(3), С. 517 - 533

Опубликована: Июнь 5, 2023

The highest risk factor for the development of neurodegenerative diseases like tauopathies is aging. Many physiological decrements underlying aging are linked to cellular senescence. Senescent cells characterized by an irreversible growth arrest and formation a senescence-associated secretory phenotype (SASP), proinflammatory secretome that modifies microenvironment contributes tissue deterioration. Microglia, innate immune in brain, can enter senescent state during In addition, microglia have been identified brains tau-transgenic mice patients suffering from tauopathies. While contribution other growing area research, effect tau on microglial senescence remains elusive. Here, we exposed primary 5 15 nanomolar (nM) monomeric 18 h, followed recovery period 48 h. Using multiple markers, found exposure nM, but not nM increased levels cell cycle DNA damage marker, induced loss nuclear envelope protein lamin B1 histone marker H3K9me3, impaired clearance migration, altered morphology resulted SASP. Taken together, show lead As were shown negatively impact pathologies, this suggests presence vicious circle, which should be further investigated future.

Язык: Английский

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AP2A1 modulates cell states between senescence and rejuvenation

Cellular Signalling, Год журнала: 2025, Номер unknown, С. 111616 - 111616

Опубликована: Янв. 1, 2025

Aging proceeds with the accumulation of senescent cells in multiple organs. These exhibit increased size compared to young cells, which promotes further senescence and age-related diseases. Currently, molecular mechanism behind maintenance such huge cell architecture undergoing remains poorly understood. Here we focus on reorganization actin stress fibers induced upon replicative human fibroblasts, widely used as a model. We identified, together our previous proteomic study, that AP2A1 (alpha 1 adaptin subunit adaptor protein 2) is upregulated along length enlarged fibers. Knockdown reversed senescence-associated phenotypes, exhibiting features cellular rejuvenation, while its overexpression advanced phenotypes. Similar functions were identified UV- or drug-induced observed epithelial well. Furthermore, found colocalized integrin β1, both proteins move linearly With observations focal adhesions are this coincides strengthened adhesion substrate, these results suggest maintain their large by reinforcing effective anchorage through β1 translocation This may work efficiently case relying random diffusion given resulting increase travel time distance for endocytosed vesicle transportation.

Язык: Английский

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