Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults

Age-related changes in ion channel expression are likely to affect neuronal signaling. Here, we examine how age affects Kv4/Shal and Kv1/Shaker K+ channel protein levels in Drosophila. We show that Kv4/Shal protein levels decline sharply from 3 days to 10 days, then more gradually from 10 to 40 days after eclosion. In contrast, Kv1/Shaker protein exhibits a transient increase at 10 days that then stabilizes and eventually declines at 40 days. We present data that begin to show a relationship between reactive oxygen species (ROS), Kv4/Shal, and locomotor performance. We show that Kv4/Shal levels are negatively affected by ROS, and that over-expression of Catalase or RNAi knock-down of the ROS-generating enzyme, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase (NOX), can attenuate the loss of Kv4/Shal protein. Finally, we compare levels of Kv4.2 and Kv4.3 in the hippocampus, olfactory bulb, cerebellum, and motor cortex of mice aged 6 weeks and 1 year. While there was no global decline in Kv4.2/4.3 that parallels what we report in Drosophila, we did find that Kv4.2/4.3 are differentially affected in various brain regions; this survey of changes may help inform mammalian studies that examine neuronal function with age.

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Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2015.0434 ◽

2016 ◽

Vol 371 (1700) ◽

pp. 20150434 ◽

Cited By ~ 38

Author(s):

Michael J. Berridge

Keyword(s):

Reactive Oxygen Species ◽

Vitamin D ◽

Neuronal Cell Death ◽

Memory Loss ◽

Neuronal Cell ◽

Reactive Oxygen ◽

Cardiac Cells ◽

Amyloid Formation ◽

Oxygen Species ◽

Age Related

Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca 2+ and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca 2+ and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer's disease (AD). In cardiac cells, this deficiency alters the Ca 2+ transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca 2+ landscape that initiates amyloid formation, which then elevates the resting level of Ca 2+ to drive the memory loss that progresses to neuronal cell death and dementia. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

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Targeting Mitochondrial Metabolism as a Strategy to Treat Senescence

Cells ◽

10.3390/cells10113003 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3003

Author(s):

Yun Haeng Lee ◽

Ji Yun Park ◽

Haneur Lee ◽

Eun Seon Song ◽

Myeong Uk Kuk ◽

...

Keyword(s):

Energy Source ◽

Reactive Oxygen Species ◽

Oxidative Phosphorylation ◽

Reactive Oxygen ◽

Mitochondrial Metabolism ◽

Metabolic Reprogramming ◽

Oxygen Species ◽

Metabolic Alterations ◽

Age Related

Mitochondria are one of organelles that undergo significant changes associated with senescence. An increase in mitochondrial size is observed in senescent cells, and this increase is ascribed to the accumulation of dysfunctional mitochondria that generate excessive reactive oxygen species (ROS). Such dysfunctional mitochondria are prime targets for ROS-induced damage, which leads to the deterioration of oxidative phosphorylation and increased dependence on glycolysis as an energy source. Based on findings indicating that senescent cells exhibit mitochondrial metabolic alterations, a strategy to induce mitochondrial metabolic reprogramming has been proposed to treat aging and age-related diseases. In this review, we discuss senescence-related mitochondrial changes and consequent mitochondrial metabolic alterations. We assess the significance of mitochondrial metabolic reprogramming for senescence regulation and propose the appropriate control of mitochondrial metabolism to ameliorate senescence. Learning how to regulate mitochondrial metabolism will provide knowledge for the control of aging and age-related pathologies. Further research focusing on mitochondrial metabolic reprogramming will be an important guide for the development of anti-aging therapies, and will provide novel strategies for anti-aging interventions.

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Effects of Aging on Cardiac Oxidative Stress and Transcriptional Changes in Pathways of Reactive Oxygen Species Generation and Clearance

Journal of the American Heart Association ◽

10.1161/jaha.120.019948 ◽

2021 ◽

Author(s):

Farhan Rizvi ◽

Claudia C. Preston ◽

Larisa Emelyanova ◽

Mohammed Yousufuddin ◽

Maria Viqar ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Complex I ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Functional Enrichment ◽

Pathway Enrichment Analysis ◽

Oxygen Species ◽

Age Related ◽

Ros Homeostasis

Background Age‐related heart diseases are significant contributors to increased morbidity and mortality. Emerging evidence indicates that mitochondria within cardiomyocytes contribute to age‐related increased reactive oxygen species (ROS) generation that plays an essential role in aging‐associated cardiac diseases. Methods and Results The present study investigated differences between ROS production in cardiomyocytes isolated from adult (6 months) and aged (24 months) Fischer 344 rats, and in cardiac tissue of adult (18–65 years) and elderly (>65 years) patients with preserved cardiac function. Superoxide dismutase inhibitable ferricytochrome c reduction assay (1.32±0.63 versus 0.76±0.31 nMol/mg per minute; P =0.001) superoxide and H 2 O 2 production, measured as dichlorofluorescein diacetate fluorescence (1646±428 versus 699±329, P =0.04), were significantly higher in the aged versus adult cardiomyocytes. Similarity in age‐related alteration between rats and humans was identified in mitochondrial‐electron transport chain‐complex‐I‐associated increased oxidative‐stress by MitoSOX fluorescence (53.66±18.58 versus 22.81±12.60; P =0.03) and in 4‐HNE adduct levels (187.54±54.8 versus 47.83±16.7 ng/mg protein, P =0.0063), indicative of increased peroxidation in the elderly. These differences correlated with changes in functional enrichment of genes regulating ROS homeostasis pathways in aged human and rat hearts. Functional merged collective network and pathway enrichment analysis revealed common genes prioritized in human and rat aging‐associated networks that underlay enriched functional terms of mitochondrial complex I and common pathways in the aging human and rat heart. Conclusions Aging sensitizes mitochondrial and extramitochondrial mechanisms of ROS buildup within the heart. Network analysis of the transcriptome highlights the critical elements involved with aging‐related ROS homeostasis pathways common in rat and human hearts as targets.

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Proteome and Secretome Dynamics of Stem Cell-Derived Retinal Pigmented Epithelium in Response to Acute and Chronic ROS

10.1101/529271 ◽

2019 ◽

Author(s):

Jesse G. Meyer ◽

Thelma Garcia ◽

Birgit Schilling ◽

Bradford W. Gibson ◽

Deepak A. Lamba

Keyword(s):

Reactive Oxygen Species ◽

Stem Cell ◽

Molecular Mechanisms ◽

Reactive Oxygen ◽

Age Related Macular Degeneration ◽

Oxygen Species ◽

Urotensin Ii ◽

Retinal Pigmented Epithelium ◽

Age Related ◽

Pigmented Epithelium

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in developed countries, and is characterized by slow retinal degeneration linked to chronic oxidative stress in the retinal pigmented epithelium (RPE). The exact molecular mechanisms that lead to RPE death and dysfunction in response to chronic reactive oxygen species (ROS) are still unclear. In this work, human stem cell-derived RPE samples were treated with a low dose of paraquat (PQ) for 1 week or 3 weeks to induce chronic reactive oxygen species (ROS) stress. Cells were then harvested and both the intracellular and secreted RPE proteomes were quantified by mass spectrometry. Inside the RPE, chronic ROS caused concerted increase of glycolytic proteins but decreased mitochondrial proteins, as well as decreased extracellular matrix proteins and membrane proteins required for endocytosis. From the secreted proteins, we found that stressed RPE secrete over 1,000 detectable proteins, and the composition of the proteins secreted from RPE changes due to chronic ROS. Notably, secreted APOE is decreased 4-fold due to 3 weeks of chronic ROS stress, and urotensin-II, the strongest known vasoconstrictor, doubles. Further, secreted TGF-beta is increased, and its cognate signaler BMP1 decreased in the secretome. Together, these alterations of the RPE proteome and protein secretome paint a detailed molecular picture of the retinal stress response in space and time.

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Mitochondrial Genome (mtDNA) Mutations that Generate Reactive Oxygen Species

Antioxidants ◽

10.3390/antiox8090392 ◽

2019 ◽

Vol 8 (9) ◽

pp. 392 ◽

Cited By ~ 12

Author(s):

Hahn ◽

Zuryn

Keyword(s):

Reactive Oxygen Species ◽

Neurodegenerative Disorders ◽

Metabolic Diseases ◽

Reactive Oxygen ◽

Oxygen Species ◽

Cellular Energy ◽

Mtdna Mutations ◽

Cellular Energy Metabolism ◽

Age Related ◽

Multiple Copies

Mitochondria are critical for the energetic demands of virtually every cellular process within nucleated eukaryotic cells. They harbour multiple copies of their own genome (mtDNA), as well as the protein-synthesing systems required for the translation of vital subunits of the oxidative phosphorylation machinery used to generate adenosine triphosphate (ATP). Molecular lesions to the mtDNA cause severe metabolic diseases and have been proposed to contribute to the progressive nature of common age-related diseases such as cancer, cardiomyopathy, diabetes, and neurodegenerative disorders. As a consequence of playing a central role in cellular energy metabolism, mitochondria produce reactive oxygen species (ROS) as a by-product of respiration. Here we review the evidence that mutations in the mtDNA exacerbate ROS production, contributing to disease.

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