Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders

Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P.; Strosznajder, Joanna B.

doi:10.1007/s11064-016-2110-y

Cited by 209 publications

(150 citation statements)

References 213 publications

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“…With this large array of protein modifying actions, it is conceivable that SIRT alterations play critical roles in multiple disease processes. Indeed, the pathogenetic role of mitochondrial SIRTs has been shown in diabetes, aging, neurodegenerative disorders, and multiple malignancies (Jęśko, Wencel, Strosznajder, & Strosznajder, 2017).…”

Section: Discussionmentioning

confidence: 99%

Glucose‐induced oxidative stress and accelerated aging in endothelial cells are mediated by the depletion of mitochondrial SIRTs

et al. 2020

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Diabetic complications cause significant morbidity and mortality. Dysfunction of vascular endothelial cells (ECs), caused by oxidative stress, is a main mechanism of cellular damage. Oxidative stress accelerates EC senescence and DNA damage. In this study, we examined the role of mitochondrial sirtuins (SIRTs) in glucose‐induced oxidative stress, EC senescence, and their regulation by miRNAs. Human retinal microvascular endothelial cells (HRECs) were exposed to 5 mmol/L (normoglycemia; NG) or 25 mmol/L glucose (hyperglycemia; HG) with or without transfection of miRNA antagomirs (miRNA‐1, miRNA‐19b, and miRNA‐320; specific SIRT‐targeting miRNAs). Expressions of SIRT3, 4 and 5 and their targeting miRNAs were examined using qRT‐PCR and ELISAs were used to study SIRT proteins. Cellular senescence was investigated using senescence‐associated β‐gal stain; while, oxidative stress and mitochondrial alterations were examined using 8‐OHdG staining and cytochrome B expressions, respectively. A streptozotocin‐induced diabetic mouse model was also used and animal retinas and hearts were collected at 2 months of diabetes. In HRECs, HG downregulated the mRNAs of SIRTs, while SIRT‐targeting miRNAs were upregulated. ELISA analyses confirmed such downregulation of SIRTs at the protein level. HG additionally caused early senescence, endothelial‐to‐mesenchymal transition and oxidative DNA damage in ECs. These changes were prevented by the transfection of specific miRNA antagomirs and by resveratrol. Retinal and cardiac tissues from diabetic mice also showed similar reductions of mitochondrial SIRTs. Collectively, these findings demonstrate a novel mechanism in which mitochondrial SIRTs regulate glucose‐induced cellular aging through oxidative stress and how these SIRTs are regulated by specific miRNAs. Identifying such mechanisms may lead to the discovery of novel treatments for diabetic complications.

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Section: Discussionmentioning

confidence: 99%

Glucose‐induced oxidative stress and accelerated aging in endothelial cells are mediated by the depletion of mitochondrial SIRTs

et al. 2020

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“…Activation of Sirt1 enables the deacetylation of a variety of proteins, resulting in a robust, protective cellular response, as it regulates processes such as cell death, metabolism or neurodegeneration [30]; while Sirt2 has been reported to regulate oxidative stress, genome integrity and myelination and its dysfunction is found in most age-related neurodegenerative disorders such as AD, Parkinson's disease and Amyotrophic Lateral Sclerosis, as well as in physiological aging [31]. Accumulated evidence indicates that Sirt6 gene expression is lower in the hippocampus and cerebral cortex of aged mice [32,33] and that it is concerned with H3K9 acetylation [32]. In reference to this family of deacetylases, our results demonstrate decreased Sirt1, Sirt2 and Sirt6 gene expression in SAMP8 mice compared to SAMR1 and SAMR1 under CMS.…”

Section: Discussionmentioning

confidence: 99%

Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

Puigoriol-Illamola

Martínez-Damas

Pallàs

2020

IJMS

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Cognitive and behavioural disturbances are a growing public healthcare issue for the modern society, as stressful lifestyle is becoming more and more common. Besides, several pieces of evidence state that environment is crucial in the development of several diseases as well as compromising healthy aging. Therefore, it is important to study the effects of stress on cognition and its relationship with aging. To address these queries, Chronic Mild Stress (CMS) paradigm was used in the senescence-accelerated mouse prone 8 (SAMP8) and resistant 1 (SAMR1). On one hand, we determined the changes produced in the three main epigenetic marks after 4 weeks of CMS treatment, such as a reduction in histone posttranslational modifications and DNA methylation, and up-regulation or down-regulation of several miRNA involved in different cellular processes in mice. In addition, CMS treatment induced reactive oxygen species (ROS) damage accumulation and loss of antioxidant defence mechanisms, as well as inflammatory signalling activation through NF-κB pathway and astrogliosis markers, like Gfap. Remarkably, CMS altered mTORC1 signalling in both strains, decreasing autophagy only in SAMR1 mice. We found a decrease in glycogen synthase kinase 3 β (GSK-3β) inactivation, hyperphosphorylation of Tau and an increase in sAPPβ protein levels in mice under CMS. Moreover, reduction in the non-amyloidogenic secretase ADAM10 protein levels was found in SAMR1 CMS group. Consequently, detrimental effects on behaviour and cognitive performance were detected in CMS treated mice, affecting mainly SAMR1 mice, promoting a turning to SAMP8 phenotype. In conclusion, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence.responses to different stimulus [1]. Indeed, normal aging differs from pathological aging and this might be explained by the lifestyle. Environmental factors drive epigenetic modifications, resulting in phenotypic differences, which alter almost all tissues and organs. Although the brain is one of the most affected structures, such modifications lead to a progressive decline in the cognitive function and create a favourable context for the development of neurodegenerative diseases [2]. Aging is the most significant risk factor for most chronic diseases, such as age-related cognitive decline and Alzheimer's disease (AD) [3]. In fact, AD is the most prevalent dementia and its progression is influenced by both genetic and environmental factors [4].Several studies define that a good environment is essential to enhance learning and cognitive abilities, besides the continued presence of stressors being associated with the opposite effects. Epigenetics refers to potentially heritable and environmentally modifiable changes in gene expression mediated via non-DNA encoded mechanisms [5]. Recent evidence has demonstrated significant associations between epigenetic alterations and stress [2,6]. Potential threats cause a course of action releasing numerous transm...

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“…2014) searching manually for the names of each epigenetic gene in GenBank (NCBI Resources Coordinators 2018) (Table S1) based on a large list of histone-modifier genes present in eukaryotes (Yun et al . 2011; Jęśko et al . 2017).…”

Section: Methodsmentioning

confidence: 99%

Queen pheromone modulates the expression of epigenetic modifier genes in the brain of honeybee workers

Junior

Ronai²,

Hartfelder³

et al. 2020

Preprint

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Pheromones are used by many insects to mediate social interactions. In the highly eusocial honeybee (Apis mellifera) queen mandibular pheromone (QMP) is involved in the regulation of reproduction and behaviour of workers. The molecular mechanisms by which QMP acts are largely unknown. Here we investigate how genes responsible for epigenetic modifications to DNA, RNA and histones respond to the presence of QMP. We show that several of these genes are upregulated in the honeybee brain when workers are exposed to QMP. This provides a plausible mechanism by which pheromone signalling may influence gene expression in the brain of honeybee workers. We propose that pheromonal communication systems, such as those used by social insects, evolved to respond to environmental signals by making use of existing epigenomic machineries.

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Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders

Cited by 209 publications

References 213 publications

Glucose‐induced oxidative stress and accelerated aging in endothelial cells are mediated by the depletion of mitochondrial SIRTs

Glucose‐induced oxidative stress and accelerated aging in endothelial cells are mediated by the depletion of mitochondrial SIRTs

Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

Queen pheromone modulates the expression of epigenetic modifier genes in the brain of honeybee workers

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