Sirtuin signaling in cellular senescence and aging

Lee, Shin‐Hae; Lee, Ji-Hyeon; Lee, Hye Yeon; Min, Kyung‐Jin

doi:10.5483/bmbrep.2019.52.1.290

Cited by 352 publications

(281 citation statements)

References 145 publications

(204 reference statements)

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“…There are seven members of the sirtuin family, SIRT1-SIRT7, which are located in different subcellular compartments. These enzymes are ubiquitously distributed from eubacteria to mammals [150]. In particular, SIRTs have been associated with various cellular and metabolic processes regulating cell plasticity mechanisms of adaptation to various stresses [151].…”

Section: Sirtuinsmentioning

confidence: 99%

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

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Section: Sirtuinsmentioning

confidence: 99%

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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“…Upregulated pathways in Sin3a-LOF AT2 cells included oxidative phosphorylation, mitochondrial dysfunction, sirtuin signaling, EIF2 signaling, and mTOR signaling. Interestingly, these pathways are all linked to cellular senescence (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).…”

Section: A Novel Mouse Model Of Conditional At2 Stem Cell Senescencementioning

confidence: 99%

Senescence of alveolar stem cells drives progressive pulmonary fibrosis

Yao

Guan

Carraro

et al. 2019

Preprint

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Tissue fibrosis is a common pathological outcome of chronic disease that markedly impairs organ function leading to morbidity and mortality. In the lung, idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Here, we show that alveolar type 2 (AT2) stem cells isolated from IPF lung tissue exhibit characteristic transcriptomic features of cellular senescence. We used conditional loss of Sin3a in adult mouse AT2 cells to initiate a program of p53-dependent cellular senescence, AT2 cell depletion, and spontaneous, progressive pulmonary fibrosis. We establish that senescence rather than loss of epithelial stem cells serves as a proximal driver of Tgfb activation and progressive fibrosis and show that either genetic or pharmacologic interventions targeting p53 activation, senescence, or downstream Tgfb activation, block fibrogenesis.

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“…Fasting regimes and SIRT1 activation have been shown to increase longevity and delay onset of disease in yeast, fruit flies, mice and more recently, non-human primate animal models (12,16,17). Fasting-induced SIRT1 activation has been linked to increased NAD + levels, increased mitochondrial biogenesis and delayed senescence (17)(18)(19). Additionally, we showed that chronic intermittent fasting prevents the development of DR and extends longevity by restructuring the microbiome of type 2 diabetic animals (20).…”

Section: Introductionmentioning

confidence: 70%

Pharmacological and fasting-induced activation of SIRT1/LXRα signaling alleviates diabetes-induced retinopathy

McFarland

et al. 2019

Preprint

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In diabetes, the retina, a tissue with unique metabolic needs, demonstrates dysregulation of the intricate balance between nutrient availability and utilization. This results in cholesterol accumulation, pro-inflammatory and pro-apoptotic changes, and consequently neurovascular damage. Sirtuin 1 (SIRT1), a nutrient sensing deacetylase, is downregulated in the diabetic retina. In this study, the effect of SIRT1 stimulation by fasting or by pharmacological activation using SRT1720, was evaluated on retinal cholesterol metabolism, inflammation and neurovascular damage. SIRT1 activation, in retinal endothelial cells (REC) and neuronal retinal progenitor cells (R28), led to Liver X Receptor alpha (LXRα) deacetylation and subsequent increased activity, as measured by increased ATP-binding cassette transporter (ABC) A1 and G1 mRNA expression. In turn, increased cholesterol export resulted in decreased REC cholesterol levels. SIRT1 activation also led to decreased inflammation. SIRT1 activation, in vivo, prevented diabetes-induced inflammation and vascular and neural degeneration.Diabetes-induced visual function impairment, as measured by electroretinogram and optokinetic response, was significantly improved as a result of SIRT1 activation. Taken together, activation of SIRT1 signaling is an effective therapeutic strategy that provides a

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Sirtuin signaling in cellular senescence and aging

Cited by 352 publications

References 145 publications

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

Senescence of alveolar stem cells drives progressive pulmonary fibrosis

Pharmacological and fasting-induced activation of SIRT1/LXRα signaling alleviates diabetes-induced retinopathy

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