Aging increases Oxidative Stress and Renal Expression of Oxidant and Antioxidant Enzymes that Are Associated with an Increased Trend in Systolic Blood Pressure

Gomes, Pedro; Simão, Sónia; Silva, Elisabete; Pinto, Vanda; Amaral, J. S.; Afonso, Joana; Serrão, Paula; Pinho, Maria João; Soares-da-Silva, Patrı́cio

doi:10.4161/oxim.2.3.8819

Cited by 60 publications

(53 citation statements)

References 42 publications

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“…ROS are known to be essential to many cell signaling pathways and likely play a key physiological role in adipose biology (5,19,20,23,57). In contrast to physiological redox signaling, deleterious oxidative stress is known to occur in many tissues with aging and is known to contribute to the deleterious changes in tissue function that are observed in many aging tissues (15,21,55,59). Our studies point to the potential for deleterious oxidative stress to occur in response to age-related increases in hypoxia.…”

Section: Discussionmentioning

confidence: 70%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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As a part of aging there are known to be numerous alterations which occur in multiple tissues of the body, and the focus of this study was to determine the extent to which oxidative stress and hypoxia occur during adipose tissue aging. In our studies we demonstrate for the first time that aging is associated with both hypoxia (38% reduction in oxygen levels, Po2 21.7 mmHg) and increases reactive oxygen species in visceral fat depots of aging male C57Bl/6 mice. Interestingly, aging visceral fat depots were observed to have significantly less change in the expression of genes involved in redox regulation compared with aging subcutaneous fat tissue. Exposure of 3T3-L1 adipocytes to the levels of hypoxia observed in aging adipose tissue was sufficient to alter multiple aspects of adipose biology inducing increased levels of in insulin-stimulated glucose uptake and decreased lipid content. Taken together, these data demonstrate that hypoxia and increased levels of reactive oxygen species occur in aging adipose tissue, highlighting the potential for these two stressors as potential modulators of adipose dysfunction during aging.

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Section: Discussionmentioning

confidence: 70%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…NADPH Oxidase 4 (Nox4) is upregulated by ROS generated from mitochondrial dysfunction, and in turn increased Nox4 also generates ROS, thereby creating a redox signaling loop (29–31). Nox4 increases with age and its expression correlates with ROS accumulation in the kidney (32, 33). For these reasons, we used Nox4 expression as a potential metric for signaling changes in response to SS-31 mitochondrial treatment.…”

Section: Resultsmentioning

confidence: 99%

The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age

Sweetwyne

Pippin

Eng

et al. 2017

Kidney International

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Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 month (equivalent to a 79 year old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31 to aged mice. Baseline (24 month-old) mice were randomized to receive 8 weeks of SS-31, or saline, and sacrificed at 26 months of age. SS-31 treatment improved age-related mitochondrial morphology and glomerulosclerosis. Assessment of glomeruli revealed that SS-31 reduced senescence (p16, senescence-associated-β-Gal) and increased the density of parietal epithelial cells. However, SS-31 treatment reduced markers of parietal epithelial cell activation (Collagen IV, pERK1/2 and α-smooth muscle actin). SS-31 did not impact podocyte density, but reduced markers of podocyte injury (desmin), and improved cytoskeletal integrity (synaptopodin). This was accompanied by higher glomerular endothelial cell density (CD31). Thus, despite initiating therapy in late-age mice, a short course of SS-31 has protective benefits on glomerular mitochondria, accompanied by temporal changes to the glomerular architecture. This systemic pharmacological intervention in old-aged animals limits glomerulosclerosis and senescence, reduces parietal epithelial cell activation, and improves podocyte and endothelial cell integrity.

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“…In addition to the aforementioned pathologic states, tissue factors such as protein, deoxyribonucleic acid, and lipid oxidation products are associated with renal aging 3,4…”

Section: Introductionmentioning

confidence: 99%

Oxidative damage parameters in renal tissues of aged and young rats based on gender

Uzun¹,

Korkmaz²,

Sitar³

et al. 2013

CIA

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PurposeAging is characterized by a gradual functional decrease of all systems including the kidneys. Growing evidence links altered lipid protein redox-homeostasis with renal dysfunction. The effect of sexual dimorphism on the lipid protein redox-homeostasis mechanisms in the aging kidney is obscure. In the current study, we aimed to investigate redox homeostasis as it related to sexual dimorphism on protein oxidation and lipid peroxidation parameters, as protein carbonyl (PCO), total thiol (T-SH), advanced oxidation protein products (AOPP), malondialdehyde, glutathione (GSH), and superoxide dismutase (SOD) activity, as potential aging biomarkers, which may contribute to an analysis of the free radical theory of aging.Materials and methodsThe study was carried out with 16 naturally aged rats (24 months old; eight males and eight females) and their corresponding young rat groups as controls (6 months old; eight males and eight females). All of the aforementioned parameters (PCO, T-SH, AOPP, MDA, GSH, SOD) were measured manually instead of automated devices or ELISA kits.ResultsPCO, AOPP, and malondialdehyde levels in aged rats were significantly higher in the older rat group than in the younger rat group, whereas SOD activities were significantly lower in old rats. T-SH levels were not significantly different in male groups; however, T-SH levels were lower in the aged female group than in the young female control group. In addition, GSH levels were significantly different between the aged rat group and the corresponding young control group for both genders.ConclusionWith respect to PCO and AOPP, impaired redox homeostasis is substantially more prominent in males than females. The decrease of G-SH levels in male groups could be attributed to stabilizing the redox status of protein thiol groups by the depletion of the GSH groups. Considering the results, the renal tissue proteins and lipids in different genders may have different susceptibilities to oxidative damage.

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Aging increases Oxidative Stress and Renal Expression of Oxidant and Antioxidant Enzymes that Are Associated with an Increased Trend in Systolic Blood Pressure

Cited by 60 publications

References 42 publications

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age

Oxidative damage parameters in renal tissues of aged and young rats based on gender

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