scholarly journals Dendranthema zawadskii var. lucidum (Nakai) J.H. Park Extract Inhibits Cellular Senescence in Human Dermal Fibroblasts and Aging-Related Inflammation in Rats

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 801
Author(s):  
Jehun Choi ◽  
Gwi-Yeong Jang ◽  
Jeonghoon Lee ◽  
Hae-Young Chung ◽  
Hyung-Jun Noh ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Cell Cycle Progression ◽  
Inflammatory Responses ◽  
Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Aged Rats ◽  
Age Related ◽  
Dendranthema Zawadskii ◽  
Beta Galactosidase

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.

scholarly journals Puerarin blocks the aging phenotype in human dermal fibroblasts

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249367
Author(s):  
Yuki Kamiya ◽  
Mao Odama ◽  
Aki Mizuguti ◽  
Shigeru Murakami ◽  
Takashi Ito
Keyword(s):  
Dermal Fibroblast ◽  
Smooth Muscle Actin ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
High Passage ◽  
Normal Human ◽  
Low Passage ◽  
Passage Cells ◽  
Beta Galactosidase ◽  
Functional Defects

Dermal fibroblast aging contributes to aging-associated functional defects in the skin since dermal fibroblasts maintain skin homeostasis by interacting with the epidermis and extracellular matrix. Here, we found that puerarin, an isoflavone present in Pueraria lobata (Kudzu), can prevent the development of the aging-phenotype in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were subcultivated and high-passage cells were selected as senescent cells, whereas low-passage cells were selected as a young cell control. Puerarin treatment increased cell proliferation and decreased the proportion of senescence-associated beta-galactosidase-positive cells in a high-passage culture of NHDFs. Moreover, puerarin treatment reduced the number of smooth muscle actin (SMA)-positive myofibroblasts and the expression of a reticular fibroblast marker, calponin 1 (CNN1), which were induced in high-passage NHDFs. Fulvestrant, an estrogen receptor antagonist, blocked the puerarin-mediated downregulation of SMA and CNN1. Our results suggest that puerarin may be a useful functional food that alleviates aging-related functional defects in dermal fibroblasts.

scholarly journals Effect of MMP/TIMP Balancing of Cynoglossus semilaevis Shell Extracts on Skin Protection

Fishes ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 34
Author(s):  
Soo-Cheol Choi ◽  
In-Ah Lee
Keyword(s):  
Skin Diseases ◽  
Dermal Fibroblast ◽  
Functional Materials ◽  
Human Dermal Fibroblast ◽  
Cynoglossus Semilaevis ◽  
Dermal Fibroblasts ◽  
Skin Tissue ◽  
Dependent Manner ◽  
Functional Material ◽  
Concentration Dependent Manner

Cynoglossus semilaevis shell is a by-product of the Cynoglossus semilaevis, a species of fish mainly distributed along the west coast of Korea. As its skin is very tough and difficult to process, it is not useful as food. For this reason, most of it is discarded except for a small amount that is used as feed, which results in environmental pollution. Considering this, there is a need for research on the development of functional materials using Cynoglossus semilaevis shell. This study focused on the mechanism of in vitro expression function of Cynoglossus semilaevis shell extract (CSE) for skin tissue in human dermal fibroblasts that induced or did not induce wrinkles by UV-B irradiation and aims to use it as a functional material for human skin beauty or wrinkle improvement through extraction and purification. According to the ELISA results using human dermal fibroblast cells, CSE reduced MMP-1 and elastase activity by up to 21.89% and 12.04%, respectively, in a concentration-dependent manner, and increased PIP synthesis by up to 62.24% in a concentration-dependent manner. The RT-PCR test results using mRNA showed the MMP-1, 2, and 3 expression levels were suppressed in the CSE-treated group compared to the UVB-induced group and caused a concentration-dependent increase in TIMP-1 in the CSE-treat group. These results suggest that CSE can maintain and improve skin tissue conditions through MMP/TIMP balancing in human dermal fibroblast cell lines and indicate its potential as a functional material for improving skin diseases and suppressing photo-aging.

scholarly journals Resolvin D1 Suppresses H2O2-Induced Senescence in Fibroblasts by Inducing Autophagy through the miR-1299/ARG2/ARL1 Axis

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1924
Author(s):  
Hyun Ji Kim ◽  
Boram Kim ◽  
Hyung Jung Byun ◽  
Lu Yu ◽  
Tuan Minh Nguyen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cellular Senescence ◽  
Vascular Endothelial Cells ◽  
Dermal Fibroblast ◽  
Fibroblast Cell ◽  
Dermal Fibroblasts ◽  
Vascular Endothelial ◽  
Yeast Two Hybrid ◽  
Resolvin D1 ◽  
Two Hybrid

ARG2 has been reported to inhibit autophagy in vascular endothelial cells and keratinocytes. However, studies of its mechanism of action, its role in skin fibroblasts, and the possibility of promoting autophagy and inhibiting cellular senescence through ARG2 inhibition are lacking. We induced cellular senescence in dermal fibroblasts by using H2O2. H2O2-induced fibroblast senescence was inhibited upon ARG2 knockdown and promoted upon ARG2 overexpression. The microRNA miR-1299 suppressed ARG2 expression, thereby inhibiting fibroblast senescence, and miR-1299 inhibitors promoted dermal fibroblast senescence by upregulating ARG2. Using yeast two-hybrid assay, we found that ARG2 binds to ARL1. ARL1 knockdown inhibited autophagy and ARL1 overexpression promoted it. Resolvin D1 (RvD1) suppressed ARG2 expression and cellular senescence. These data indicate that ARG2 stimulates dermal fibroblast cell senescence by inhibiting autophagy after interacting with ARL1. In addition, RvD1 appears to promote autophagy and inhibit dermal fibroblast senescence by inhibiting ARG2 expression. Taken together, the miR-1299/ARG2/ARL1 axis emerges as a novel mechanism of the ARG2-induced inhibition of autophagy. Furthermore, these results indicate that miR-1299 and pro-resolving lipids, including RvD1, are likely involved in inhibiting cellular senescence by inducing autophagy.

scholarly journals Puerarin blocks aging phenotype in cultured human dermal fibroblasts

2020 ◽  
Author(s):  
Yuki Kamiya ◽  
Mao Odama ◽  
Aki Mizuguti ◽  
Shigeru Murakami ◽  
Takashi Ito
Keyword(s):  
Dermal Fibroblast ◽  
Smooth Muscle Actin ◽  
Dermal Fibroblasts ◽  
Pueraria Lobata ◽  
Human Dermal Fibroblasts ◽  
Proliferating Cells ◽  
Food Factor ◽  
High Passage ◽  
Beta Galactosidase ◽  
Functional Defects

AbstractDermal fibroblast aging contributes to aging-associated functional defects in the skin since dermal fibroblasts are important to maintain skin homeostasis by interacting with epidermis and extracellular matrix. Here we identified that puerarin, an isoflavone contained in Pueraria lobata (Kudzu), can prevent the aging-phenotype of human dermal fibroblasts. Puerarin treatment increased in proliferating cells and decreased in senescence-associated beta-galactosidase positive cells in the high-passage culture of dermal fibroblasts. Moreover, puerarin reduced smooth muscle actin-positive myofibroblasts and the expression of a reticular fibroblast marker, calponin 1 (CNN1), which were induced in high-passage fibroblasts. Fulvestrant, an estrogen receptor antagonist, blocked puerarin-mediated downregulation of SMA and CNN1. Our results suggest that puerarin may be a useful food factor that alleviates aging-related functional defects in the skin.

scholarly journals Autophagy Dysfunction, Cellular Senescence, and Abnormal Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic Potential

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Shoubi Wang ◽  
Xiaoran Wang ◽  
Yaqi Cheng ◽  
Weijie Ouyang ◽  
Xuan Sang ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Prevention And Treatment ◽  
Wet Amd

Age-related macular degeneration (AMD) is a blinding disease caused by multiple factors and is the primary cause of vision loss in the elderly. The morbidity of AMD increases every year. Currently, there is no effective treatment option for AMD. Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) is currently the most widely used therapy, but it only aims at neovascularization, which is an intermediate pathological phenomenon of wet AMD, not at the etiological treatment. Anti-VEGF therapy can only temporarily delay the degeneration process of wet AMD, and AMD is easy to relapse after drug withdrawal. Therefore, it is urgent to deepen our understanding of the pathophysiological processes underlying AMD and to identify integrated or new strategies for AMD prevention and treatment. Recent studies have found that autophagy dysfunction in retinal pigment epithelial (RPE) cells, cellular senescence, and abnormal immune-inflammatory responses play key roles in the pathogenesis of AMD. For many age-related diseases, the main focus is currently the clearing of senescent cells (SNCs) as an antiaging treatment, thereby delaying diseases. However, in AMD, there is no relevant antiaging application. This review will discuss the pathogenesis of AMD and how interactions among RPE autophagy dysfunction, cellular senescence, and abnormal immune-inflammatory responses are involved in AMD, and it will summarize the three antiaging strategies that have been developed, with the aim of providing important information for the integrated prevention and treatment of AMD and laying the ground work for the application of antiaging strategies in AMD treatment.

scholarly journals Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keng Siang Lee ◽  
Shuxiao Lin ◽  
David A. Copland ◽  
Andrew D. Dick ◽  
Jian Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Cellular Senescence ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Age Related

AbstractAge-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Besides the association of innate immune pathway genes with AMD susceptibility, environmental stress- and cellular senescence-induced alterations in pathways such as metabolic functions and inflammatory responses are also implicated in the pathophysiology of AMD. Cellular senescence is an adaptive cell process in response to noxious stimuli in both mitotic and postmitotic cells, activated by tumor suppressor proteins and prosecuted via an inflammatory secretome. In addition to physiological roles in embryogenesis and tissue regeneration, cellular senescence is augmented with age and contributes to a variety of age-related chronic conditions. Accumulation of senescent cells accompanied by an impairment in the immune-mediated elimination mechanisms results in increased frequency of senescent cells, termed “chronic” senescence. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD.

Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis

2021 ◽  
pp. 1-16
Author(s):  
Bing Si Li ◽  
Ri Zhe Zhu ◽  
Seok-Hee Lim ◽  
Jae Ho Seo ◽  
Byung-Min Choi
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Lung Diseases ◽  
Molecular Mechanisms ◽  
Driving Mechanism ◽  
Dependent Manner ◽  
Aging Effects ◽  
Chronic Lung Diseases ◽  
Age Related ◽  
The Impact

Oxidative stress-induced cellular senescence is now regarded as an important driving mechanism in chronic lung diseases-particularly chronic obstructive pulmonary disease (COPD). 4′,5,7-trihydroxyflavone (Apigenin) is a natural flavonoid product abundantly present in fruits, vegetables, and Chinese medicinal herbs. It has been known that apigenin has anti-oxidant, anti-inflammatory and liver-protecting effects. The efficacy of apigenin for lung aging, however, has not been reported. In this study, we selected the hydrogen peroxide (H2O[Formula: see text]- or doxorubicin (DOXO)-induced senescence model in WI-38 human embryonic lung fibroblast cells to determine the potential anti-aging effects of apigenin in vitro and associated molecular mechanisms. We found that apigenin reduced senescence-associated [Formula: see text]-galactosidase (SA-[Formula: see text]-gal) activity and promoted cell growth, concomitant with a decrease in levels of Acetyl (ac)-p53, p21[Formula: see text], and p16[Formula: see text] and an increase in phospho (p)-Rb. Apigenin also increased the activation ratio of silent information regulator 1 (SIRT1), nicotinamide adenine dinucleotide (NAD[Formula: see text], and NAD[Formula: see text]/NADH and inhibited cluster of differentiation 38 (CD38) activity in a concentration-dependent manner. SIRT1 inhibition by SIRT1 siRNA abolished the anti-aging effect of apigenin. In addition, CD38 inhibition by CD38 siRNA or apigenin increased the SIRT1 level and reduced H2O2-induced senescence. Our findings suggest that apigenin is a promising phytochemical for reducing the impact of senescent cells in age-related lung diseases such as COPD.

scholarly journals Inhibition of 3-phosphoinositide–dependent protein kinase 1 (PDK1) can revert cellular senescence in human dermal fibroblasts

2020 ◽  
Vol 117 (49) ◽  
pp. 31535-31546
Author(s):  
Sugyun An ◽  
Si-Young Cho ◽  
Junsoo Kang ◽  
Soobeom Lee ◽  
Hyung-Su Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cellular Senescence ◽  
Nuclear Factor Κb ◽  
Dermal Fibroblasts ◽  
Quiescent State ◽  
Human Dermal Fibroblasts ◽  
Dependent Protein Kinase ◽  
Age Related ◽  
Dependent Protein

Cellular senescence is defined as a stable, persistent arrest of cell proliferation. Here, we examine whether senescent cells can lose senescence hallmarks and reenter a reversible state of cell-cycle arrest (quiescence). We constructed a molecular regulatory network of cellular senescence based on previous experimental evidence. To infer the regulatory logic of the network, we performed phosphoprotein array experiments with normal human dermal fibroblasts and used the data to optimize the regulatory relationships between molecules with an evolutionary algorithm. From ensemble analysis of network models, we identified 3-phosphoinositide–dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. We showed that inhibition of PDK1 in senescent human dermal fibroblasts eradicates senescence hallmarks and restores entry into the cell cycle by suppressing both nuclear factor κB and mTOR signaling, resulting in restored skin regeneration capacity. Our findings provide insight into a potential therapeutic strategy to treat age-related diseases associated with the accumulation of senescent cells.

scholarly journals Mechanisms of Androgen Receptor Agonist- and Antagonist-Mediated Cellular Senescence in Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1833 ◽  
Author(s):  
Miriam Kokal ◽  
Kimia Mirzakhani ◽  
Thanakorn Pungsrinont ◽  
Aria Baniahmad
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cellular Senescence ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Cell Senescence ◽  
Dependent Manner ◽  
Androgen Levels

The androgen receptor (AR) plays a leading role in the control of prostate cancer (PCa) growth. Interestingly, structurally different AR antagonists with distinct mechanisms of antagonism induce cell senescence, a mechanism that inhibits cell cycle progression, and thus seems to be a key cellular response for the treatment of PCa. Surprisingly, while physiological levels of androgens promote growth, supraphysiological androgen levels (SAL) inhibit PCa growth in an AR-dependent manner by inducing cell senescence in cancer cells. Thus, oppositional acting ligands, AR antagonists, and agonists are able to induce cellular senescence in PCa cells, as shown in cell culture model as well as ex vivo in patient tumor samples. This suggests a dual AR-signaling dependent on androgen levels that leads to the paradox of the rational to keep the AR constantly inactivated in order to treat PCa. These observations however opened the option to treat PCa patients with AR antagonists and/or with androgens at supraphysiological levels. The latter is currently used in clinical trials in so-called bipolar androgen therapy (BAT). Notably, cellular senescence is induced by AR antagonists or agonist in both androgen-dependent and castration-resistant PCa (CRPC). Pathway analysis suggests a crosstalk between AR and the non-receptor tyrosine kinase Src-Akt/PKB and the PI3K-mTOR-autophagy signaling in mediating AR-induced cellular senescence in PCa. In this review, we summarize the current knowledge of therapeutic induction and intracellular pathways of AR-mediated cellular senescence.

scholarly journals Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

2021 ◽  
Vol 9 ◽  
Author(s):  
Ruchi Kumari ◽  
Parmjit Jat
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cellular Senescence ◽  
Molecular Mechanisms ◽  
Growth Arrest ◽  
Dependent Manner ◽  
Tissue Repair And Regeneration ◽  
Cycle Arrest ◽  
Age Related ◽  
Secretory Phenotype

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stimuli, as well as developmental signals. Senescence is considered to be a highly dynamic, multi-step process, during which the properties of senescent cells continuously evolve and diversify in a context dependent manner. It is associated with multiple cellular and molecular changes and distinct phenotypic alterations, including a stable proliferation arrest unresponsive to mitogenic stimuli. Senescent cells remain viable, have alterations in metabolic activity and undergo dramatic changes in gene expression and develop a complex senescence-associated secretory phenotype. Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging. Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span. Senescence can also act as a potent anti-tumor mechanism, by preventing proliferation of potentially cancerous cells. It is a cellular program which acts as a double-edged sword, with both beneficial and detrimental effects on the health of the organism, and considered to be an example of evolutionary antagonistic pleiotropy. Activation of the p53/p21WAF1/CIP1 and p16INK4A/pRB tumor suppressor pathways play a central role in regulating senescence. Several other pathways have recently been implicated in mediating senescence and the senescent phenotype. Herein we review the molecular mechanisms that underlie cellular senescence and the senescence associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.

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