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1.
Rev. Ciênc. Saúde ; 13(1): 3-13, Março 2023.
Article in English, Portuguese | LILACS | ID: biblio-1444157

ABSTRACT

Objetivo: Avaliar as características de programas de exercício físico para idosos e seus efeitos durante a pandemia de COVID-19. Métodos: revisão integrativa, realizada entre os meses de janeiro a março de 2022. As buscas foram realizadas no MEDLINE via PubMed, Lilacs via BVS, PEDro e Cochrane Library. Foram incluídos artigos experimentais (ensaios clínicos randomizados, ensaios não randomizados ou estudos quase-experimentais) publicados de 2019 a 2021, sem restrição de idioma, e que utilizaram programas de exercício físico para idosos (> 60 anos) em sua intervenção. A seleção dos estudos foi realizada através da leitura de título e resumo, e seguida da leitura do texto completo. Os artigos selecionados tiveram seus resultados extraídos com auxílio de um formulário on-line, tabulados com a utilização de planilha eletrônica e analisados qualitativa e quantitativamente. Resultados: Foram identificados 113 estudos; 7 preencheram os critérios de elegibilidade e foram incluídos na revisão, todos ensaios clínicos randomizados. Os programas de exercícios foram em maior frequência, multicomponente (resistência, equilíbrio, flexibilidade e aeróbico), entregues de forma on -line, sendo realizados de 2 a 7 vezes na semana, com duração entre 30 e 50 min. Efeitos significativos foram observados na função física, composição corporal, triglicerídeo sanguíneo, incidência de quedas, atividade física e capacidade funcional.Conclusões: Os programas de exercício físico utilizados durante a pandemia da COVID-19 apresentaram resultados promissores para a população idosa, se mostrando uma alternativa viável para a manutenção das funções físicas, mentais e cognitivas dos idosos em momentos de calamidade pública.


Objective: To evaluate the characteristics of physical exercise programs for older adults and their effects during the COVID-19 pandemic. Methods: An integrative review was conducted between January and March 2022. A search was conducted in MEDLINE via PubMed, Lilacs via BVS, PEDro, and Cochrane Library. Experimental articles (randomized clinical trials, non-randomized trials, or quasi-experimental studies) published from 2019 to 2021, with no language restriction, and that used physical exercise programs for older adults (> 60 years) in their intervention were included. The studies were selected by reading the title, abstract, and full text. The selected articles had their results extracted using an online form, tabulated using an electronic spreadsheet, and analyzed qualitatively and quantitatively. Results: 113 studies were identified; 7 met the eligibility criteria and were included in the review, all randomized controlled trials. The multi-component exercise programs were more frequent (resistance, balance, flexibility, and aerobic), delivered remotelyand performed 2 to 7 times a week, lasting between 30 and 50 minutes. Significant effects were observed on physical function, body composition, blood triglycerides, the incidence of falls, physical activity, and functional capacity. Conclusions: The physical exercise programs used during the COVID-19 pandemic showed promising results for older adults. The programs proved to be a viable alternative for maintaining the physical, mental, and cognitive functions of older adults in times of public calamity.


Subject(s)
Humans , Male , Female , Aged , Aged , Exercise , Coronavirus , Pandemics , COVID-19 , Triglycerides , Aging , Randomized Controlled Trials as Topic , Review , Cellular Senescence , Database , Sedentary Behavior
2.
Protein & Cell ; (12): 202-216, 2023.
Article in English | WPRIM | ID: wpr-982531

ABSTRACT

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.


Subject(s)
Humans , Mesenchymal Stem Cells/physiology , Cellular Senescence , Homeostasis , Cell Cycle Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Mitochondria/metabolism , Electron Transport Complex III/metabolism , Cells, Cultured
3.
Journal of Zhejiang University. Science. B ; (12): 101-114, 2023.
Article in English | WPRIM | ID: wpr-971473

ABSTRACT

Given its state of stable proliferative inhibition, cellular senescence is primarily depicted as a critical mechanism by which organisms delay the progression of carcinogenesis. Cells undergoing senescence are often associated with the alteration of a series of specific features and functions, such as metabolic shifts, stemness induction, and microenvironment remodeling. However, recent research has revealed more complexity associated with senescence, including adverse effects on both physiological and pathological processes. How organisms evade these harmful consequences and survive has become an urgent research issue. Several therapeutic strategies targeting senescence, including senolytics, senomorphics, immunotherapy, and function restoration, have achieved initial success in certain scenarios. In this review, we describe in detail the characteristic changes associated with cellular senescence and summarize currently available countermeasures.


Subject(s)
Humans , Cellular Senescence , Carcinogenesis , Immunotherapy , Aging , Tumor Microenvironment
4.
Journal of Central South University(Medical Sciences) ; (12): 153-164, 2022.
Article in English | WPRIM | ID: wpr-929018

ABSTRACT

OBJECTIVES@#Liver cancer is the sixth most common malignant tumor in the world. Hepatocellular carcinoma (HCC) accounts for 85%-90% of all patients with liver cancer. It possesses the characteristics of insidious onset, rapid progression, early recurrence, easy drug resistance, and poor prognosis. NIMA related kinase 2 (NEK2) is a cell cycle regulating kinases, which regulates cell cycle in mitosis. Cellular senescence is a complex heterogeneous process, and is a stable form of cell cycle arrest that limits the proliferative potential of cells. This study aims to investigate the relationship between the expression level of NEK2 and the senescence in hepatoma cells, and to explore the effect of NEK2 expression on hepatoma cell senescence and the underlying molecular mechanism.@*METHODS@#A total of 581 senescence-relevant genes were obtained from the GenAge website. The gene expression data of tumor tissues of 370 HCC patients were downloaded from the Cancer Genome Atlas database. The co-expression of NEK2 and aging-related genes was analyzed by R-package. KEGG was used to analyze the significant gene enrichment pathway of differentially expressed genes in NEK2 overexpression HEK293. The stable transfected cell lines with overexpression and knockdown of NEK2 were constructed in hepatoma cell line SMMC-7721 and HepG2, and senescence-associated β-galactosidase (SA-β-gal) staining was used to detect senescence, the cell proliferation was detected by CCK-8 method and clone formation experiment, the cell cycle was analyzed by flow cytometry, and the expression of proteins related to p53/p21, p16/Rb, and phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signal transduction pathway was detected by Western blotting.@*RESULTS@#There were 320 senescence related genes co-expressed with NEK2. KEGG analysis showed that the senescence signaling pathway was significantly enriched in HEK293 cells with overexpression of NEK2.Compared with SMMC-7721 or HepG2 without knockdown of NEK2, the senescent cells of SMMC-7721 and HepG2 with knockdown of NEK2 were increased, cell proliferation and clone formation were decreased significantly, the percentage of cells in G0/G1 phase was increased, the expression levels of phospho-Akt (p-Akt) and phospho-Rb (p-Rb) protein were decreased significantly, and the expression level of p16 protein was increased significantly (all P<0.05). Compared with SMMC-7721 or HepG2 transfected with blank plasmid, the senescent cells of SMMC-7721 and HepG2 overexpressing NEK2 were decreased, the cell proliferation and clone formation were increased significantly, the percentage of cells in G0/G1 phase were decreased, the expression levels of p-Akt and p-Rb protein were increased significantly, and the expression level of p16 protein was decreased significantly (all P<0.05).@*CONCLUSIONS@#NEK2 may mediate the anti-aging effect of hepatoma cells through p16/Rb and PTEN/Akt signal transduction pathways, which provides a new theoretical basis for NEK2 to promote the progress of liver cancer and a new idea for the targeting treatment for liver cancer.


Subject(s)
Humans , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/physiology , Cellular Senescence/genetics , HEK293 Cells , Liver Neoplasms/pathology , NIMA-Related Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism
5.
International Journal of Oral Science ; (4): 29-29, 2022.
Article in English | WPRIM | ID: wpr-939848

ABSTRACT

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.


Subject(s)
Humans , Cellular Senescence/genetics , Immunoglobulin G/metabolism , Interleukin-13/pharmacology , Mitochondria/metabolism , Sialadenitis/metabolism
6.
Acta Physiologica Sinica ; (6): 479-488, 2022.
Article in Chinese | WPRIM | ID: wpr-939582

ABSTRACT

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.


Subject(s)
Humans , Aging/pathology , Cellular Senescence , Lung/pathology , Lung Diseases/pathology , Respiration Disorders/pathology , Telomere , Telomere Shortening
7.
Acta Physiologica Sinica ; (6): 469-478, 2022.
Article in Chinese | WPRIM | ID: wpr-939581

ABSTRACT

Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can self-renew and differentiate. Numerous studies have shown that MSCs have important roles in areas such as regenerative medicine and tissue engineering. However, it is worth noting that MSCs will gradually age during long-term in vitro expansion with decreased stemness such as weakened migration ability, slowed proliferation rate and decreased differentiation potential, which greatly hinders the application of MSCs. Currently, the microenvironment for cell growth is recognized as one of the factors causing senescence in MSCs. Recent studies point out that the latest technologies such as exogenous administration, oxygen concentration regulation and extracellular matrix (ECM) construction can delay stem cell senescence by simulating or regulating the microenvironment. Here, we review the current knowledge of the characteristics and molecular mechanisms of senescent MSCs and microenvironment strategies to maintain MSCs stemness, which can provide a reference for future large-scale application of MSCs preparations in tissue engineering and clinical studies.


Subject(s)
Cell Differentiation , Cell Proliferation , Cells, Cultured , Cellular Senescence , Extracellular Matrix , Mesenchymal Stem Cells
8.
Journal of Zhejiang University. Medical sciences ; (6): 95-101, 2022.
Article in English | WPRIM | ID: wpr-928660

ABSTRACT

Cellular senescence is a biological process associated with the degeneration of cell structure and function, which contribute to age-related diseases. Atherosclerosis is a chronic inflammatory disease that can cause a variety of cardiovascular disorders. In this article, we review the effects of cellular senescence on the development of atherosclerosis through diverse physiopathological changes, focusing on the alterations in senescent organelles and the increased senescence-associated secretory phenotype (SASP), and exploring the relevant therapeutic strategies for atherosclerosis by clearing senescent cells and reducing SASP, to provide new insights for the treatment of atherosclerosis.


Subject(s)
Humans , Aging , Atherosclerosis , Cardiovascular Diseases , Cellular Senescence , Chronic Disease , Senescence-Associated Secretory Phenotype
9.
International Journal of Oral Science ; (4): 11-11, 2021.
Article in English | WPRIM | ID: wpr-880865

ABSTRACT

Hyperglycemia induces chronic low-grade inflammation (inflammaging), which is a newly identified contributor to diabetes-related tissue lesions, including the inflammatory bone loss in periodontitis. It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype (SASP). Macrophage is a key SASP-spreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment. Using a transgenic diabetic model (BLKS/J-Lepr


Subject(s)
Animals , Mice , Cellular Senescence , Diabetes Mellitus, Experimental , Glucose Transporter Type 1 , Inflammation , Macrophages
10.
China Journal of Chinese Materia Medica ; (24): 6216-6223, 2021.
Article in Chinese | WPRIM | ID: wpr-921779

ABSTRACT

This study aims to explore the effect of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma(hereinafter referred to as GNS) on the SIRT1-autophagy pathway of endothelial cell senescence induced by hydrogen peroxide(H_2O_2). To be specific, vascular endothelial cells were classified into the blank control group(control), model group(model), model + DMSO group(DMSO), resveratrol group(RESV), and GNS low-dose(GNS-L), medium-dose(GNS-M), and high-dose(GNS-H) groups. They were treated with H_2O_2 for senescence induction except the control. After intervention of cells in each group with corresponding drugs for 24 h, cell growth status was observed under an inverted microscope, and the formation of autophagosome under the transmission electron microscope. In addition, the changes of microtubule-associated protein 1 light chain 3β(LC3 B) were detected by immunofluorescence staining. The autophagy flux was tracked with the autophagy double-labeled adenovirus(mRFP-GFP-LC3) fusion protein. Dansylcadaverine(MDC) staining was employed to determine the autophagic vesicles, and Western blot the expression of sirtuin 1(SIRT1), ubiquitin-binding protein p62, and LC3Ⅱ. After H_2O_2 induction, cells demonstrated slow growth, decreased adhesion ability, raised number of SA-β-gal-stained blue ones, a certain number of autophagosomes with bilayer membrane and secondary lysosomes in the cytoplasm, and slight rise of autophagy flux level. Compared with the model group, GNS groups showed improved morphology, moderate adhesion ability, complete and smooth membrane, decreased SA-β-gal-stained blue cells, many autophagosomes, autophagic vesicles, and secondary lysosomes in the cytoplasm, increased autophagolysosomes, autophagy flux level, and fluorescence intensity of LC3 B and MDC, up-regulated expression of SIRT1 and LC3Ⅱ, and down-regulated expression of p62, suggesting the improvement of autophagy level. GNS can delay the senescence of vascular endothelial cells. After the intervention, the autophagy flux and related proteins SIRT1, LC3Ⅱand p62 changed significantly, and the autophagy level increased significantly. However, EX527 weakened the effect of Chinese medicine in delaying vascular senescence. GNS may delay the senescence of vascular endothelial cells through the SIRT1 autophagy pathway.


Subject(s)
Autophagy , Cells, Cultured , Cellular Senescence , Drugs, Chinese Herbal/pharmacology , Endothelial Cells/drug effects , Hydrogen Peroxide , Panax/chemistry , Sirtuin 1/genetics
11.
Acta Physiologica Sinica ; (6): 828-834, 2021.
Article in Chinese | WPRIM | ID: wpr-921286

ABSTRACT

As a kind of mental illness, depression produces great difficulties in clinical diagnosis and treatment, and has a high disability rate. It is urgent to clarify the mechanism of depression to find potential therapeutic targets and effective clinical treatment methods. As a deacetylase, silent mating type information regulator 2 homolog 1 (SIRT1) is involved in many biological processes such as cell aging, cancer, and cardiovascular disease. In recent years, more and more studies have found that SIRT1 gene plays an important role in the pathogenesis of depression, but the mechanism is still unclear. Therefore, this review mainly summarizes the relevant research progress on the role and mechanism of SIRT1 gene in the hippocampus, prefrontal cortex, amygdala, hypothalamic suprachiasmatic nucleus, and nucleus accumbens in depression, in order to provide new ideas for exploring the mechanism and prevention of depression.


Subject(s)
Humans , Cellular Senescence , Depression/genetics , Hippocampus/metabolism , Nucleus Accumbens , Sirtuin 1/metabolism
12.
Journal of Experimental Hematology ; (6): 1002-1006, 2021.
Article in Chinese | WPRIM | ID: wpr-880183

ABSTRACT

Emerging data have demonstrated that bone marrow mesenchymal stem cells (MSCs) play important roles in the progression of myelodysplastic syndrome (MDS). Experiments in vitro have showed that MSCs derived from MDS patients (MDS-MSC) exhibit the biological characteristics of cell senescence. Although the underlying mechanisms that regulate cell senescence need to be further elucidated, existing researches indicate that the mechanisms of MDS-MSC senescence have significant heterogeneity. Depth understanding of the underlying mechanisms involved in cell senescence of MDS-MSC are crucial to explore the potential therapeutic target of MDS. Therefore, this review summarizes research advances related with MSC senescence, such as MDS-MSC intrinsic changes in telomere shortening, DNA methylation status, oxidative stress and signal pathways regulating cell senescence in recent years.


Subject(s)
Humans , Bone Marrow , Bone Marrow Cells , Cellular Senescence , Mesenchymal Stem Cells , Myelodysplastic Syndromes
13.
Arch. med ; 20(1): 188-202, 2020-01-18.
Article in Spanish | LILACS | ID: biblio-1053281

ABSTRACT

El ejercicio ha demostrado efectividad para promover la plasticidad cerebral en los procesos de envejecimiento neural. Esta revisión narrativa de literatura tiene como objetivo analizar el efecto neural del ejercicio para promover la plasticidad cerebral en el envejecimiento. Los resultados incluyeron publicaciones que mencionan los efectos de la plasticidad cerebral mediada por el ejercicio empleando protocolos de ejercicio con duración, intensidad y frecuencia clínicamente significativa. La revisión documental se organizó en tres apartados: a) envejecimiento neural y procesos fisiológicos interrelacionados, b) plasticidad cerebral mediada por el ejercicio, c) ejercicio para promover el envejecimiento neural saludable. Se pudo concluir que el fisioterapeuta, aplicando protocolos de ejercicio, puede promover cambios positivos en la función cerebral lo cual se traducen en la mejoría del desempeño físico y funcional de los adultos mayores..(AU)


Exercise has shown effectiveness in promoting brain plasticity in neural aging processes.This narrative review of literature aims to analyze the neural effect of exercise to promote brain plasticity in aging. The results included publications that mention the effects of brain plasticity mediated by exercise, using exercise protocols with clinically significant duration, intensity and frequency. Through the documentary review three sections were determined: Neural Aging: Interrelated physiological processes; Exercisemediated brain plasticity; Exercise to promote healthy neural aging. It was concluded that the physiotherapist, applying exercise protocols, can promote positive changes in brain function, which translates into an improvement in the physical and functional performance of older adults..(AU)


Subject(s)
Cellular Senescence , Physical Therapists
14.
Acta Physiologica Sinica ; (6): 426-432, 2020.
Article in Chinese | WPRIM | ID: wpr-827045

ABSTRACT

The purpose of the present study was to investigate the effects of forkhead box O4 (FOXO4) on the senescence of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSCs were induced to senescence by natural passage, and FOXO4 expression was inhibited by lentiviral shRNA transfection. The hallmark of cell senescence was analyzed by β-galactosidase staining, and the cell viability was assayed by CCK-8 method. Flow cytometry was used to investigate the apoptosis of hUC-MSCs. The expression levels of Bcl-2, Bax, FOXO4, interleukin 6 (IL-6) and cleaved Caspase-3 were detected by qPCR and Western blot. Immunofluorescence staining was used to detect FOXO4 expression. The amount of IL-6 secreted by hUC-MSCs was detected by ELISA. The results showed that, compared with the passage 1, senescent hUC-MSCs showed up-regulated expression levels of Bax and FOXO4, down-regulated expression levels of Bcl-2 and cleaved Caspase-3, and increased IL-6 mRNA expression and secretion. FOXO4 inhibition in senescent hUC-MSCs promoted cell apoptosis, reduced cell viability, and inhibited the mRNA expression and secretion of IL-6. These results suggest that FOXO4 maintains viability and function of senescent hUC-MSCs by repressing their apoptosis response, thus accelerating senescence of the whole cell colony.


Subject(s)
Humans , Apoptosis , Cell Cycle Proteins , Cell Survival , Cellular Senescence , Forkhead Transcription Factors , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Transcription Factors , Umbilical Cord
15.
The Korean Journal of Physiology and Pharmacology ; : 69-79, 2020.
Article in English | WPRIM | ID: wpr-787137

ABSTRACT

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H₂O₂) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.


Subject(s)
Aging , AMP-Activated Protein Kinases , Apoptosis , Cardiovascular Diseases , Cellular Senescence , Hydrogen Peroxide , Muscle, Smooth, Vascular , Polyphenols , Quercetin , Risk Factors , RNA, Small Interfering
16.
Journal of Lipid and Atherosclerosis ; : 79-91, 2020.
Article in English | WPRIM | ID: wpr-786080

ABSTRACT

Cell-proliferation potency is limited, as cells cannot proceed through the cell cycle continually. Instead, they eventually show an irreversible arrest of proliferation, commonly referred to as cellular senescence. Following the initial discovery of this phenomenon by Hayflick et al., studies have indicated that cells are also destined to undergo aging. In addition to the irreversible termination of proliferation, senescent cells are characterized by a flattened and enlarged morphology. Senescent cells become pro-inflammatory and contribute to the initiation and maintenance of sustained chronic sterile inflammation. Aging is associated with the accumulation of senescent cells in the cardiovascular system, and in general these cells are considered to be pathogenic because they mediate vascular remodeling. Recently, genetic and pharmacological approaches have enabled researchers to eliminate senescent cells both in vitro and in vivo. The term “senolysis” is now used to refer to the depletion of senescent cells, and evidence indicates that senolysis contributes to the reversal of age-related pathogenic phenotypes without the risk of tumorigenesis. The concept of senolysis has opened new avenues in research on aging, and senolysis may be a promising therapeutic approach for combating age-related disorders, including arterial diseases.


Subject(s)
Aging , Carcinogenesis , Cardiovascular System , Cellular Senescence , Cell Cycle , In Vitro Techniques , Inflammation , Phenotype , Vascular Remodeling
17.
Einstein (Säo Paulo) ; 18: eAO5236, 2020. graf
Article in English | LILACS | ID: biblio-1133772

ABSTRACT

ABSTRACT Objective To follow the expansion of mesenchymal stem cells from umbilical cords by two classic senescence markers, p16 (INK4A) and p21 (CDKN1A), using practical, fast, and less expensive methods than the gold standard Western blotting technique, to evaluate its applicability in the laboratory. Methods Mesenchymal stem cells from umbilical cords were isolated from Wharton's jelly and, after quality control, morphological and immunophenotypic characterization by flow cytometry, were expanded in culture until coming close to cell cycle arrest (replicative senescence). Results A comparison was made between young cells, at passage 5, and pre-senescent cells, at passage 10, evaluating the protein expression of the classic cell senescence markers p16 and p21, comparing the results obtained by Western blotting with those obtained by flow cytometry and indirect immunofluorescence. Conclusion Follow-up of cell cultures, through indirect p16 immunofluorescence, allows the identification of mesenchymal stem cells from umbilical cord cultures at risk of reaching replicative senescence.


RESUMO Objetivo Acompanhar a expansão de células-tronco mesenquimais de cordão umbilical por dois marcadores clássicos de senescência, p16 (INK4A) e p21 (CDKN1A), usando métodos práticos, rápidos e com custo menor do que a técnica padrão-ouro de Western blotting, para avaliar sua aplicabilidade em laboratório. Métodos Células-tronco mesenquimais de cordão umbilical foram isoladas da geleia de Wharton e, após controle de qualidade e caracterização morfológica e imunofenotípica por citometria de fluxo, foram expandidas em cultura, até chegarem próximas à parada do ciclo celular (senescência replicativa). Resultados Foi feita a comparação entre células jovens, na passagem 5, e células pré-senescentes, na passagem 10, avaliando a expressão proteica dos marcadores clássicos de senescência celular p16 e p21, comparando os resultados obtidos por Western blotting com os obtidos por citometria de fluxo e imunofluorescência indireta. Conclusão O seguimento de culturas celulares, por meio da imunofluorescência indireta de p16, permite identificar as culturas de células-tronco mesenquimais de cordão umbilical em risco de atingirem a senescência replicativa.


Subject(s)
Humans , Umbilical Cord/physiology , Fluorescent Antibody Technique/methods , Cellular Senescence , Mesenchymal Stem Cells/physiology , Flow Cytometry/methods , Biomarkers/blood , Cells, Cultured , Blotting, Western , Cyclin-Dependent Kinase Inhibitor p16 , Cyclin-Dependent Kinase Inhibitor p21
18.
Journal of Southern Medical University ; (12): 1784-1792, 2020.
Article in Chinese | WPRIM | ID: wpr-880803

ABSTRACT

OBJECTIVE@#To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells.@*METHODS@#Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting.@*RESULTS@#Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 (@*CONCLUSIONS@#Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.


Subject(s)
Humans , Cell Cycle , Cell Cycle Checkpoints , Cellular Senescence , Epithelial Cells , Piperazines/pharmacology , Pyridines/pharmacology , Tumor Suppressor Protein p53/genetics
19.
Obstetrics & Gynecology Science ; : 199-211, 2019.
Article in English | WPRIM | ID: wpr-760655

ABSTRACT

A better understanding of the underlying mechanisms by which signals from the fetus initiate human parturition is required. Our recent findings support the core hypothesis that oxidative stress (OS) and cellular senescence of the fetal membranes (amnion and chorion) trigger human parturition. Fetal membrane cell senescence at term is a natural physiological response to OS that occurs as a result of increased metabolic demands by the maturing fetus. Fetal membrane senescence is affected by the activation of the p38 mitogen activated kinase-mediated pathway. Similarly, various risk factors of preterm labor and premature rupture of the membranes also cause OS-induced senescence. Data suggest that fetal cell senescence causes inflammatory senescence-associated secretory phenotype (SASP) release. Besides SASP, high mobility group box 1 and cell-free fetal telomere fragments translocate from the nucleus to the cytosol in senescent cells, where they represent damage-associated molecular pattern markers (DAMPs). In fetal membranes, both SASPs and DAMPs augment fetal cell senescence and an associated ‘sterile’ inflammatory reaction. In senescent cells, DAMPs are encapsulated in extracellular vesicles, specifically exosomes, which are 30–150 nm particles, and propagated to distant sites. Exosomes traffic from the fetus to the maternal side and cause labor-associated inflammatory changes in maternal uterine tissues. Thus, fetal membrane senescence and the inflammation generated from this process functions as a paracrine signaling system during parturition. A better understanding of the premature activation of these signals can provide insights into the mechanisms by which fetal signals initiate preterm parturition.


Subject(s)
Female , Humans , Pregnancy , Aging , Cellular Senescence , Cytosol , Exosomes , Extracellular Vesicles , Extraembryonic Membranes , Fetus , Inflammation , Membranes , Obstetric Labor, Premature , Oxidative Stress , Paracrine Communication , Parturition , Phenotype , Premature Birth , Risk Factors , Rupture , Telomere
20.
Korean Circulation Journal ; : 615-626, 2019.
Article in English | WPRIM | ID: wpr-759447

ABSTRACT

BACKGROUND AND OBJECTIVES: Angiotensin II (Ang II) has been suggested to accelerate vascular senescence, however the molecular mechanism(s) remain unknown. METHODS: We cultured human coronary artery smooth muscle cells (hCSMCs) and treated Ang II and/or fimasartan. Or we transfected adenoviral vectors expressing CYR61 (Ad-CYR61) or antisense CYR61 (Ad-As-CYR61). Cellular senescence was evaluated senescence-associated β-galactosidase (SA-β-gal) assay. The molecular mechanisms were investigated real-time PCR and western blots. RESULTS: SA-β-gal-positive cells significantly increased in Ang II-treated hCSMCs (5.77±1.43-fold compared with the control). The effect of Ang II was significantly attenuated by pretreatment with the Ang II type 1 receptor blocker, fimasartan (2.00±0.92-fold). The expression of both p53 and p16 senescence regulators was significantly increased by Ang II (p53: 1.39±0.17, p16: 1.19±0.10-fold vs. the control), and inhibited by fimasartan. Cysteine-rich angiogenic protein 61 (CYR61) was rapidly induced by Ang II. Compared with the control, Ad-CYR61-transfected hCSMCs showed significantly increased SA-β-gal-positive cells (3.47±0.65-fold). Upon transfecting Ad-AS-CYR61, Ang II-induced senescence (3.74±0.23-fold) was significantly decreased (1.77±0.60-fold). p53 expression by Ang II was significantly attenuated by Ad-AS-CYR61, whereas p16 expression was not regulated. Ang II activated ERK1/2 and p38 MAPK, which was significantly blocked by fimasartan. ERK and p38 inhibition both regulated Ang II-induced CYR61 expression. However, p53 expression was only regulated by ERK1/2, whereas p16 expression was only attenuated by p38 MAPK. CONCLUSIONS: Ang II induced vascular senescence by the ERK/p38 MAPK–CYR61 pathway and ARB, fimasartan, protected against Ang II-induced vascular senescence.


Subject(s)
Humans , Aging , Angiotensin II Type 1 Receptor Blockers , Angiotensin II , Angiotensins , Blotting, Western , Cellular Senescence , Coronary Vessels , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , p38 Mitogen-Activated Protein Kinases , Real-Time Polymerase Chain Reaction , Receptor, Angiotensin, Type 1
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