Giant Multinucleated Cells in Aging and Senescence—An Abridgement

Kloc, Małgorzata; Uosef, Ahmed; Subuddhi, Arijita; Kubiak, Jacek Z.; Piprek, Rafał P.; Ghobrial, Rafik M.

doi:10.3390/biology11081121

Cited by 15 publications

(8 citation statements)

References 80 publications

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“…Our data show that myeloid‐derived cells (macrophages and giant cells) are the major inflammatory infiltrating cells expressing p16 and p21. Indeed, giant cell formation has been linked to senescence and has been suggested as a potential target in treatments promoting longevity (12). However, not all giant cells expressed p16 or p21, suggesting that not all of these cells were senescent.…”

Section: Discussionmentioning

confidence: 99%

Indication of Activated Senescence Pathways in the Temporal Arteries of Patients With Giant Cell Arteritis

Jiemy

Sleen

Graver

et al. 2023

Arthritis & Rheumatology

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ObjectiveGiant cell arteritis (GCA) affects almost exclusively individuals above 50 years old, suggesting a role of aging‐related changes such as cellular senescence in its pathobiology. The kinases p21(WAF1/CIP1) and p16/INK4A play key roles in 2 distinct pathways leading to senescence. The proinflammatory molecules interleukin‐6 (IL‐6) and granulocyte–macrophage colony‐stimulating factor (GM‐CSF), which are key components of the senescence‐associated secretory phenotype (SASP), are effective targets of treatment in GCA. Here, we aimed to investigate the presence of p21+ and p16+ cells producing these SASP cytokines in temporal artery biopsies (TABs) of patients with GCA.MethodsEight patients with GCA and 14 age‐matched, non‐GCA individuals who underwent a TAB were included. Immunohistochemical staining of p21, p16, IL‐6, and GM‐CSF was performed. Multiplex immunofluorescent staining was performed to investigate the colocalization of p21 and p16 with IL‐6, GM‐CSF, and immune cell markers (CD68, CD3, CD20).ResultsWe found that expression levels of p16, p21, IL‐6, and GM‐CSF were elevated in the TABs of patients with GCA. Both p16‐ and p21‐expressing cells were mainly found near the internal lamina elastica, especially among giant cells and macrophages, although p21 and p16 expression could be found in all 3 layers of the vessels. Expression of p16 and p21 was occasionally found in T cells but not B cells. The p16+ and p21+ cells expressing GM‐CSF/IL‐6 were detected throughout the TABs.ConclusionOur data suggest the presence of activated senescence pathways at the site of vascular inflammation in GCA and support further research into the role of senescence in the pathophysiology of GCA.

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Section: Discussionmentioning

confidence: 99%

Indication of Activated Senescence Pathways in the Temporal Arteries of Patients With Giant Cell Arteritis

Jiemy

Sleen

Graver

et al. 2023

Arthritis & Rheumatology

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“…There remain numerous reports of its adverse effects on the phenotype of the cell or organism. Senescent cells are usually flattened and form giant multinucleated cells (GMCs), where metabolic deregulation, chromatin rearrangement, and resistance to apoptotic stimuli occur ( 19 ). Currently, more evidence has linked the tumor progression with the senescent microenvironment, which is mainly attributed to the SASP expression.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer

Han

Deng²,

Yang³

et al. 2023

Front. Immunol.

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BackgroundProstate cancer (PCa) is an age-associated malignancy with high morbidity and mortality rate, posing a severe threat to public health. Cellular senescence, a specialized cell cycle arrest form, results in the secretion of various inflammatory mediators. In recent studies, senescence has shown an essential role in tumorigenesis and tumor development, yet the extensive effects of senescence in PCa have not been systematically investigated. Here, we aimed to develop a feasible senescence-associated prognosis model for early identification and appropriate management in patients with PCa.MethodThe RNA sequence results and clinical information available from The Cancer Genome Atlas (TCGA) and a list of experimentally validated senescence-related genes (SRGs) from the CellAge database were first obtained. Then, a senescence-risk signature related with prognosis was constructed using univariate Cox and LASSO regression analysis. We calculated the risk score of each patient and divided them into high-risk and low-risk groups in terms of the median value. Furthermore, two datasets (GSE70770 and GSE46602) were used to assess the effects of the risk model. A nomogram was built by integrating the risk score and clinical characteristics, which was further verified using ROC curves and calibrations. Finally, we compared the differences in the tumor microenvironment (TME) landscape, drug susceptibility, and the functional enrichment among the different risk groups.ResultsWe established a unique prognostic signature in PCa patients based on eight SRGs, including CENPA, ADCK5, FOXM1, TFAP4, MAPK, LGALS3, BAG3, and NOX4, and validated well prognosis-predictive power in independent datasets. The risk model was associated with age and TNM staging, and the calibration chart presented a high consistency in nomogram prediction. Additionally, the prognostic signature could serve as an independent prediction factor due to its high accuracy. Notably, we found that the risk score was positively associated with tumor mutation burden (TMB) and immune checkpoint, whereas negatively correlated with tumor immune dysfunction and exclusion (TIDE), suggesting that these patients with risk scores were more sensitive to immunotherapy. Drug susceptibility analysis revealed differences in the responses to general drugs (docetaxel, cyclophosphamide, 5-Fluorouracil, cisplatin, paclitaxel, and vincristine) were yielded between the two risk groups.ConclusionIdentifying the SRG-score signature may become a promising method for predicting the prognosis of patients with PCa and tailoring appropriate treatment strategies.

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“…It has been suggested that cofilin1 is associated with changes in cell morphology [ 14 ]. The nuclei of senescent ECs also undergo changes, such as increased nucleus size, multinucleation, and dissipation of the nuclear membrane [ 15 , 16 ].…”

Section: The Phenotype Of Senescent Ecsmentioning

confidence: 99%

Endothelial Senescence in Neurological Diseases

Xiao¹,

Jiang²,

Wei³

et al. 2023

Aging and disease

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Endothelial cells, which are highly dynamic cells essential to the vascular network, play an indispensable role in maintaining the normal function of the body. Several lines of evidence indicate that the phenotype associated with senescent endothelial cells causes or promotes some neurological disorders. In this review, we first discuss the phenotypic changes associated with endothelial cell senescence; subsequently, we provide an overview of the molecular mechanisms of endothelial cell senescence and its relationship with neurological disorders. For refractory neurological diseases such as stroke and atherosclerosis, we intend to provide some valid clues and new directions for clinical treatment options.

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Giant Multinucleated Cells in Aging and Senescence—An Abridgement

Cited by 15 publications

References 80 publications

Indication of Activated Senescence Pathways in the Temporal Arteries of Patients With Giant Cell Arteritis

Indication of Activated Senescence Pathways in the Temporal Arteries of Patients With Giant Cell Arteritis

Identification of a novel senescence-associated signature to predict biochemical recurrence and immune microenvironment for prostate cancer

Endothelial Senescence in Neurological Diseases

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