Age-dependent guanine oxidation in DNA of different brain regions of Wistar rats and prematurely aging OXYS rats

Sattarova, Evgeniya A.; Синицына, О. И.; Vasyunina, E. A.; Duzhak, A. B.; Kolosova, N. G.; Zharkov, Dmitry O.; Nevinsky, Georgy A.

doi:10.1016/j.bbagen.2013.01.027

Cited by 13 publications

(7 citation statements)

References 72 publications

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“…Those aged over 45 years also tended to have increased CSF levels of the DNA damage marker 8-OHdG. These data are consistent with previous results from both our laboratory and others showing that DNA and lipid oxidation increase with age in multiple organs, including the brain in animals [11], [12], [24], [43]. While limited research has been conducted within the CNS of living humans, an age related accumulation in markers of both oxidative damage (8-OHdG) and inflammation (IL-6) has been previously reported in postmortem brain tissue [9], [44].…”

Section: Discussionsupporting

confidence: 91%

Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid

et al. 2014

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An extensive body of evidence indicates that oxidative stress and inflammation play a central role in the degenerative changes of systemic tissues in aging. However a comparatively limited amount of data is available to verify whether these processes also contribute to normal aging within the brain. High levels of oxidative damage results in key cellular changes including a reduction in available nicotinamide adenine dinucleotide (NAD+), an essential molecule required for a number of vital cellular processes including DNA repair, immune signaling and epigenetic processing. In this study we quantified changes in [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8-OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy humans across a wide age range (24–91 years). CSF was collected from consenting patients who required a spinal tap for the administration of anesthetic. CSF of participants aged >45 years was found to contain increased levels of lipid peroxidation (F2-isoprostanes) (p = 0.04) and inflammation (IL-6) (p = 0.00) and decreased levels of both total antioxidant capacity (p = 0.00) and NAD(H) (p = 0.05), compared to their younger counterparts. A positive association was also observed between plasma [NAD(H)] and CSF NAD(H) levels (p = 0.03). Further analysis of the data identified a relationship between alcohol intake and CSF [NAD(H)] and markers of inflammation. The CSF of participants who consumed >1 standard drink of alcohol per day contained lower levels of NAD(H) compared to those who consumed no alcohol (p<0.05). An increase in CSF IL-6 was observed in participants who reported drinking >0–1 (p<0.05) and >1 (p<0.05) standard alcoholic drinks per day compared to those who did not drink alcohol. Taken together these data suggest a progressive age associated increase in oxidative damage, inflammation and reduced [NAD(H)] in the brain which may be exacerbated by alcohol intake.

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Section: Discussionsupporting

confidence: 91%

Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid

et al. 2014

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“…Several-fold increase of 8-oxo-dG in nuclear DNA of old compared to young animals has been observed in major organs [206,207]. Intriguingly, studies conducted both on mice and on rats suggest that nervous tissue displays the highest accumulation of 8-oxo-dG during the aging process [208,209]. Furthermore, measures of urinary secreted 8-oxo-G confirmed in human the aging-associated increase of this adduct [210].…”

Section: -Oxo-dg During Aging and Tissue Remodelingmentioning

confidence: 99%

On the epigenetic role of guanosine oxidation

et al. 2020

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Chemical modifications of DNA and RNA regulate genome functions or trigger mutagenesis resulting in aging or cancer. Oxidations of macromolecules, including DNA, are common reactions in biological systems and often part of regulatory circuits rather than accidental events.DNA alterations are particularly relevant since the unique role of nuclear and mitochondrial genome is coding enduring and inheritable information. Therefore, an alteration in DNA may represent a relevant problem given its transmission to daughter cells. At the same time, the regulation of gene expression allows cells to continuously adapt to the environmental changes that occur throughout the life of the organism to ultimately maintain cellular homeostasis.Here we review the multiple ways that lead to DNA oxidation and the regulation of mechanisms activated by cells to repair this damage. Moreover, we present the recent evidence suggesting that DNA damage caused by physiological metabolism acts as epigenetic signal for regulation of gene expression. In particular, the predisposition of guanine to oxidation might reflect an adaptation to improve the genome plasticity to redox changes.

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“… 12 , 13 It has also been reported that 8-oxoG modifications are associated with other diseases such as neurodegenerative and ageing-associated disorders. 14 – 17 …”

Section: Introductionmentioning

confidence: 99%

Genome-wide Profiling of 8-Oxoguanine Reveals Its Association with Spatial Positioning in Nucleus

et al. 2014

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8-Oxoguanine (8-oxoG) is one of the most common DNA lesions generated by reactive oxygen species. In this study, we analysed the genome-wide distribution profile of 8-oxoG by combining immunoprecipitation by antibodies specific for the DNA fragments containing 8-oxoG with a microarray that covers rat genome. Genome-wide mapping of 8-oxoG in normal rat kidney revealed that 8-oxoG is preferentially located at gene deserts. We did not observe differences in 8-oxoG levels between groups of genes with high and low expression, possibly because of the generally low 8-oxoG levels in genic regions compared with gene deserts. The distribution of 8-oxoG and lamina-associated domains (LADs) were strongly correlated, suggesting that the spatial location of genomic DNA in the nucleus determines the susceptibility to oxidative modifications. One possible explanation for high 8-oxoG levels in LADs is that the nuclear periphery is more susceptible to the oxidative damage caused by the extra-nuclear factors. Moreover, LADs have a rather compact conformation, which may limit the recruitment of repair components to the modified bases.

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Age-dependent guanine oxidation in DNA of different brain regions of Wistar rats and prematurely aging OXYS rats

Cited by 13 publications

References 72 publications

Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid

Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid

On the epigenetic role of guanosine oxidation

Genome-wide Profiling of 8-Oxoguanine Reveals Its Association with Spatial Positioning in Nucleus

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