Autophagy, Cellular Aging and Age-related Human Diseases

Cheon, So Yeong; Kim, Hyun-Jeong; Rubinsztein, David C.; Lee, Jong Eun

doi:10.5607/en.2019.28.6.643

Cited by 66 publications

(49 citation statements)

References 167 publications

(207 reference statements)

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“…Whether the membrane-bound or intracellular localization of CysLTR1 indicates that the receptor plays a role in distinct mechanisms or has a functional dependency should be clarified in future studies. ER/oxidative stress induction by H 2 O 2 treatment for a short period, which also affects autophagic activity 44 , increased CysLTR1 expression at the mRNA level; however, the amount of CysLTR1 protein did not differ between untreated and H 2 O 2 -treated (3 h) cells. Receptor mRNA transcription, protein translation, localization and degradation are very dynamic processes that permanently affect mRNA/protein levels and may explain the observed discrepancy between mRNA and protein levels following H 2 O 2 treatment.…”

Section: Discussionmentioning

confidence: 87%

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Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells

Koller

Bruckner

Aigner

et al. 2020

Sci Rep

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The retinal pigment epithelium (RPE), which is among the tissues in the body that are exposed to the highest levels of phagocytosis and oxidative stress, is dependent on autophagy function. Impaired autophagy and continuous cellular stress are associated with various disorders, such as dry age-related macular degeneration (AMD), a disease for which effective therapies are lacking. Cysteinyl leukotriene receptor (CysLTR) 1 is a potential modulator of autophagy; thus, the aim of this study was to investigate the role of CysLTR1 in autophagy regulation in the RPE cell line ARPE-19. The polarized ARPE-19 monolayer exhibited expression of CysLTR1, which was colocalized with β-tubulin III. In ARPE-19 cells, autophagic activity was rhythmically regulated and was increased upon CysLTR1 inhibition by Zafirlukast (ZK) treatment. H2O2 affected the proautophagic regulatory effect of ZK treatment depending on whether it was applied simultaneously with or prior to ZK treatment. Furthermore, mRNA levels of genes related to the leukotriene system, autophagy and the unfolded protein response were positively correlated. As CysLTR1 is involved in autophagy regulation under basal and oxidative stress conditions, a dysfunctional leukotriene system could negatively affect RPE functions. Therefore, CysLTR1 is a potential target for new treatment approaches for neurodegenerative disorders, such as AMD.

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Section: Discussionmentioning

confidence: 87%

“…Autophagy dysfunction and cellular stress increase with age and are associated with various diseases, including neurodegenerative disorders 43 , 44 . RPE cells are exposed to high levels of phagocytosis and oxidative stress; hence, functional autophagy is essential for ensuring the integrity of the RPE 22 .…”

Section: Discussionmentioning

confidence: 99%

Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells

Koller

Bruckner

Aigner

et al. 2020

Sci Rep

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“…Interestingly, autophagy and proteasome activity both decline with age [155,156], and abrogating the proteotoxic load extends lifespan. Autophagy failure has been associated with aging-related diseases like neurodegeneration or cancer [157]. Conversely, maintenance of an accurate autophagic activity contributes to lifespan extension.…”

Section: Loss Of Proteostasis Network In Agingmentioning

confidence: 99%

Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

et al. 2020

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Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.

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“…The dysregulation of autophagy has been associated with a variety of human diseases, including vascular, pulmonary, intestinal, infectious, metabolic, and neurodegenerative diseases, as well as in aging and a variety of cancer types. 25,70,71 Autophagy has a significant but controversial role in tumor development. 72 At the early stage, tumorigenesis has an initial protective role against cell differentiation, apoptosis, and proliferation of cancer cells.…”

Section: The Role Of Autophagy In Sgc Developmentmentioning

confidence: 99%

Autophagy and salivary gland cancer: A putative target for salivary gland tumors

et al. 2020

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Salivary gland carcinomas are a group of heterogeneous tumors of different histological subtypes, presenting relatively low incidence but the entire variable of types. Although novel treatment options for salivary gland carcinomas patients’ outcomes have improved, the treatment of this type of cancer is still not standardized. In addition, a significant number of patients, with a lack of optimal treatment strategies, have reduced survival. In the last two decades, a plethora of evidence pointed to the importance of autophagy, an essential catabolic process of cytoplasmatic component digestion, in cancer. In vitro and in vivo studies highlight the importance of autophagy in salivary gland carcinomas development as a tumor suppressor or promoter mechanism. Despite the potential of autophagy in salivary gland carcinomas development, no therapies are currently available that specifically focus on autophagy modulation in salivary gland carcinomas. In this review, we summarize current knowledge and clinical trials in regard to the interplay between autophagy and the development of salivary gland carcinomas. Autophagy manipulation may be a putative therapeutic strategy for salivary gland carcinomas patients.

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Autophagy, Cellular Aging and Age-related Human Diseases

Cited by 66 publications

References 167 publications

Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells

Cysteinyl leukotriene receptor 1 modulates autophagic activity in retinal pigment epithelial cells

Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

Autophagy and salivary gland cancer: A putative target for salivary gland tumors

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