• Molecules and Cells
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• v.46 no.11
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• pp.655-663
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• 2023

Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, and chronic infections. Additionally, the decline in autophagic activity contributes to tissue and organ dysfunction and aging-related diseases. Several factors, such as down-regulation of autophagy components and activators, oxidative damage, microinflammation, and impaired autophagy flux, are linked to autophagy decline. An autophagy flux impairment (AFI) has been implicated in neurological disorders and in certain other pathological conditions. Here, to enhance our understanding of AFI, we conducted a comprehensive literature review of findings derived from two well-studied cellular stress models: glucose deprivation and replicative senescence. Glucose deprivation is a condition in which cells heavily rely on oxidative phosphorylation for ATP generation. Autophagy is activated, but its flux is hindered at the autolysis step, primarily due to an impairment of lysosomal acidity. Cells undergoing replicative senescence also experience AFI, which is also known to be caused by lysosomal acidity failure. Both glucose deprivation and replicative senescence elevate levels of reactive oxygen species (ROS), affecting lysosomal acidification. Mitochondrial alterations play a crucial role in elevating ROS generation and reducing lysosomal acidity, highlighting their association with autophagy dysfunction and disease conditions. This paper delves into the underlying molecular and cellular pathways of AFI in glucose-deprived cells, providing insights into potential strategies for managing AFI that is driven by lysosomal acidity failure. Furthermore, the investigation on the roles of mitochondrial dysfunction sheds light on the potential effectiveness of modulating mitochondrial function to overcome AFI, offering new possibilities for therapeutic interventions.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.39 no.3
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• pp.177-186
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• 2013

Skin dermal fibroblast is the major collagen-producing cell type in human skin. As aging process continues in human skin, collagen production is reduced and fragmentation is increased, which is initiated by matrix metalloproteinase-1 (MMP-1). This imbalance of collagen homeostasis impairs the structure and function of dermal collagenous extracellular matrix (ECM), thereby promoting skin aging. Cysteine-rich protein 61 (CCN1), a member of the CCN family, negatively regulates collagen homeostasis in primary human skin dermal fibroblast cells. It is known in aging fibroblast cells that elevated CCN1 expression substantially reduces type I procollagen and concurrently increases MMP-1, which initiates fibrillar collagen degradation. And proliferation rate of aging fibroblast cells is reduced compared to the pre-aging fibroblast cells. In this study, we confirmed that the replicative senescence dermal fibroblast cells increased the expression levels of MMP-1 and decreased the production of type I procollagen. Our results also showed that the replicative senescence dermal fibroblast cells increased in the expression of CCN1 and decreased in the proliferation rate. Hydrolyzed Ulva pertusa extracts are the materials to improve photo-aging by reducing the expression of MMP-1 that was increased by ultraviolet and by promoting the synthesis of new collagen from fibroblast cells. In this study, we also investigated the hydrolyzed U. pertusa extract to see whether it inhibits CCN1 protein expression in the senescence fibroblasts. Results showed that the hydrolyzed U. pertusa extract inhibited the expression of MMP-1 and increased the production of type I procollagen in the aging skin fibroblast cells cultured. In addition, the proteins that regulate collagen homeostasis CCN1 expression were greatly reduced. The hydrolyzed U. pertusa extract increased the proliferation rate of the aging fibroblast cells. These results suggest that replicative senescent fibroblast cells may be used in the study of cosmetic ingredients as a model of the natural aging. In conclusion, the hydrolyzed U. pertusa extract can be used in anti-wrinkle functional cosmetic material to improve the natural aging skin care as well as photo-aging.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.102-111
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• 2020

Nitric oxide (NO)-induced protein S-nitrosylation triggers mitochondrial dysfunction and was related to cell senescence. However, the exact mechanism of these damages is not clear. In the present study, to investigate the relationship between in vitro aging and NO-induced protein S-nitrosylation, oocytes were treated with sodium nitroprusside dihydrate (SNP), and the resultant S-nitrosylated proteins were detected through biotin-switch assay. The results showed that levels of protein S-nitroso thiols (SNO)s and expression of S-nitrosoglutathione reductase (GSNOR) increased, while activity and function of mitochondria were impaired during oocyte aging. Addition of SNP, a NO donor, to the oocyte culture led to accelerated oocyte aging, increased mitochondrial dysfunction and damage, apoptosis, ATP deficiency, and enhanced ROS production. These results suggested that the increased NO signal during oocyte aging in vitro, accelerated oocyte degradation due to increased protein S-nitrosylation, and ROS-related redox signaling.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.208-218
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• 1998

To clarify the activating effects of Buthus martensi Karsch on immunological function, its effect on primary and secondary antibodies production in mice of various ages was investigated. Buthus martensi Karsch increased the number of both antibody producing cells(anti-IgM and anti-IgG producing plaque forming cells, PFC) and phagocytic activity of peritoneal macrophage. Futhermore, these phenomena were significantly increased with aging in mice. Buthus martensi Karsch also increased natural killer cell activity concerning to cancer immunology. These results suggest that Buthus martensi Karsch markedly increases the reduced activity in the elderly and activates the immune response in senescence mice.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.477-487
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• 1998

To clarify the activating effects of Scolopendrae corpus on immunological function, its effect on primary and secondary antibodies production in mice of various ages was investigated. Scolopendrae corpus increased the number of both antibody producing cells(anti-IgM and anti-IgG producing plaque forming cells, PFC) and phagocytic activity of peritoneal macrophage. Futhermore, these phenomena were significantly increased with aging in mice. Scolopendrae corpus also increased natural killer cell activity concerning to cancer immunology. These results suggest that Scolopendrae corpus markedly increases the reduced activity in the elderly and activates the immune response in senescence mice.

• BMB Reports
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• v.56 no.2
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• pp.84-89
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• 2023

The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation.

• Tuberculosis and Respiratory Diseases
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• v.69 no.5
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• pp.323-330
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• 2010

A key mechanism in the pathogenesis of chronic obstructive pulmonary disease is thought to be an abnormal inflammatory response in the lungs to the inhalation of toxic particles and gases, derived from tobacco smoke, air pollution, and/or occupational exposures. This review highlights the potential participation of several alternative pathogenetic processes, particularly involving the potential participation of biological and pathobiological processes related to aging, including oxidative stress and enhanced expression of markers of senescence/aging in emphysematous lungs, and the potential for enhanced tissue destruction involving alveolar cell apoptosis.

• Journal of Society of Preventive Korean Medicine
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• v.8 no.1
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• pp.115-133
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• 2004

Hasuohwan(何首烏丸) composed of Polygonum multiflorum Thunb and some medical herbs are known as formula of senescence delay effect. The aim of this study is to investigate the effect of Hasuohwan(何首烏丸) on antioxidant enzyme activity such as Thiobarbituric acid reactive substance(TBARS) in rat plasma and liver, Superoxide dismutase(SOD), Glutathione peroxidase(GSH-px), Catalase(CAT) in rat erythrocyte and liver. Rats were sacrificed and TBARS was measured in rat plasma and liver. SOD, GSH-px and CAT were measured in rat erythrocytes and liver. TBARS in plasma concentrations of HSO group was significantly lower than those of control group. RBC and liver GSH-px activities of HSO group were significantly higher than those of control group. According to above results, it is considered that Hasuohwan is effective in inhibiting lipid peroxidation and increasing antioxidative enzyme activities in D-galactose induced aging rat. Therefore, Hsuohwan is considered in effective of senescence delay.

• Journal of Ginseng Research
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• v.36 no.1
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• pp.78-85
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• 2012

Endothelial progenitor cells (EPC) are a population of cells that circulate in the blood stream. They play a role in angiogenesis and, therefore, can be prognostic markers of vascular repair. Ginsenoside $Rg_3$ prevents endothelial cell apoptosis through the inhibition of the mitochondrial caspase pathway. It also affects estrogen activity, which reduces EPC senescence. Sun ginseng (SG), which is heat-processed ginseng, has a high content of ginsenosides. The purpose of this study was to investigate the protective effects of SG on senescence-associated apoptosis in EPCs. In order to isolate EPCs, mononuclear cells of human blood buffy coats were cultured and characterized by their uptake of acetylated low-density lipoprotein (acLDL) and their binding of Ulex europaeus agglutinin I (ulex-lectin). Flow cytometry with annexin-V staining was performed in order to assess early and late apoptosis. Senescence was determined by ${\beta}$-galactosidase (${\beta}$-gal) staining. Staining with 4'-6-Diamidino-2-phenylindole verified that most adherent cells (93${\pm}$2.7%) were acLDL-positive and ulex-lectin-positive. The percentage of ${\beta}$-gal-positive EPCs was decreased from 93.8${\pm}$2.0% to 62.5${\pm}$3.6% by SG treatment. A fluorescence-activated cell sorter (FACS) analysis showed that 4.9% of EPCs were late apoptotic in controls. Sun ginseng decreased the apoptotic cell population by 39% in the late stage of apoptosis from control baseline levels. In conclusion, these results show antisenescent and antiapoptotic effects of SG in human-derived EPCs, indicating that SG can enhance EPC-mediated repair mechanisms.

• Journal of Radiation Protection and Research
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• v.36 no.3
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• pp.119-126
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• 2011

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging, and contributes to harmful effects in cultured cells and animal tissues. mtDNA biogenesis genes (NRF-1, TFAM) are essential for the maintenance of mtDNA, as well as the transcription and replication of mitochondrial genomes. Considering that oxidative stress is known to affect mitochondrial biogenesis, we hypothesized that ionizing radiation (IR)-induced reactive oxygen species (ROS) causes mtDNA deletion by modulating the mitochondrial biogenesis, thereby leading to cellular senescence. Therefore, we examined the effects of IR on ROS levels, cellular senescence, mitochondrial biogenesis, and mtDNA deletion in IMR-90 human lung fibroblast cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated at 4 or 8 Gy. Old cells at PD55, and H2O2-treated young cells at PD 39, were compared as a positive control. The IR increased the intracellular ROS level, senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity, and mtDNA common deletion (4977 bp), and it decreased the mRNA expression of NRF-1 and TFAM in IMR-90 cells. Similar results were also observed in old cells (PD 55) and $H_2O_2$-treated young cells. To confirm that a increase in ROS level is essential for mtDNA deletion and changes of mitochondrial biogenesis in irradiated cells, the effects of N-acetylcysteine (NAC) were examined. In irradiated and $H_2O_2$-treated cells, 5 mM NAC significantly attenuated the increases of ROS, mtDNA deletion, and SA-${\beta}$-gal activity, and recovered from decreased expressions of NRF-1 and TFAM mRNA. These results suggest that ROS is a key cause of IR-induced mtDNA deletion, and the suppression of the mitochondrial biogenesis gene may mediate this process.