Oligonol promotes anti-aging pathways <i>via</i> modulation of SIRT1-AMPK-Autophagy Pathway

Park, Seul Ki; Seong, Rak Kyun; Kim, Ji Ae; Kim, Young-Hoon; Yokozawa, Takako; Shin, Ok Sarah

doi:10.4162/nrp.2016.10.1.3

Cited by 27 publications

(26 citation statements)

References 41 publications

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“…CR may decrease the presence of ROS in neurones by increasing levels of the ROS scavengers cytochrome‐C oxidase and citrate synthase . In support of this, a SIRT1 activating compound, oligonol, increases expression of superoxide dismutase 2, a mitochondrial antioxidant …”

Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 88%

“…36,49 Moreover, oligonol, a compound known to induce SIRTs, causes an increase in microtubule-associated protein 1 light chain 3 (LC-3) (a marker of autophagy) and phosphorylation of AMPK. 50 However, the interactions between AMPK and SIRTs are complex because SIRT1 can also increase the activity of AMPK, 51 suggesting that a positive-feedback loop may exist to either prolong or potentiate the activation of autophagy. SIRTs are reported to activate autophagy through their histone deacetylase activity.…”

Section: Cr and Autophagymentioning

confidence: 99%

“…94 In support of this, a SIRT1 activating compound, oligonol, increases expression of superoxide dismutase 2, a mitochondrial antioxidant. 50 Although the multiple pathways and processes described above combine to determine the response of the cell to CR, it is still not clear how cells detect changes in whole organism energy balance. However, there is increased understanding of the role that circulating hormones play in mediating adaptations to changes in the environment.…”

Section: Cr and Mitochondrial Healthmentioning

confidence: 99%

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Less is more: Caloric regulation of neurogenesis and adult brain function

Morgan

Andrews

Davies

2017

J Neuroendocrinology

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Calorie intake is essential for regulating normal physiological processes and is fundamental to maintaining life. Indeed, both extremes of calorie intake result in increased morbidity and mortality. In this review, we discuss the effect of calorie intake on adult brain function, with an emphasis on the beneficial effects of mild calorie restriction.Recent findings relating to the regenerative and protective effects of the gastrointestinal hormone, ghrelin, suggest that it may underlie the beneficial effects of calorie restriction. We discuss the putative cellular mechanisms underlying the action of ghrelin and their possible role in supporting healthy brain ageing. K E Y W O R D Sacyl-ghrelin, adult hippocampal neurogenesis, calorie restriction, diet-induced obesity | INTRODUCTIONThe energy status of an organism is tightly controlled around a setpoint by hormonal and neural systems. These neuroendocrine checks and balances promote homeostasis, thereby ensuring an appropriate energy supply for the energetic demands of metabolism, physical activity, growth and repair.Disturbances to this homeostasis result in multiple physiological impairments, including age-related conditions such as type 2 dibetes mellitus and obesity. Perhaps less well recognised are the consequences of metabolic dysfunction on neuronal health and cognition.Diet-induced obesity (DIO) is a risk factor for neurodegenerative diseases such as Parkinson's disease (PD) and dementia. Conversely, calorie restriction (CR) (ie, an approximate 30% reduction in calorie intake) protects against neurodegeneration and promotes cognitive function (Figure 1). Indeed, there is a growing body of work supporting the CR paradigm as a tool for promoting lifespan and, perhaps more importantly, healthspan.1 However, the physiological mechanisms underlying these effects are not fully understood. Here, we review literature that identifies calorie intake as an important regulator of nerve cell function, with important implications for neurodegenerative disorders. Moreover, we describe recent research showing that CR promotes new neurone formation (neurogenesis) and neuroprotection in the adult brain and discuss the possible mechanisms that underpin this effect. | CALORIE RESTRICTION REGULATES BRAIN FUNCTIONCalorie restriction, in the absence of malnutrition, has beneficial effects on brain function, including reducing the incidence of age-related neurodegenerative disease, 2 eliciting anti-depressant behaviour 3 and improving memory function in rodents. 4 In nonhuman primates, prolonged CR in adulthood decreases the incidence of age-related disease, including measures of brain atrophy and glucose regulation. 5-7Translation of the carefully controlled CR experiments from preclinical models to humans is problematic. In particular, it is difficult to re-capitulate experimental controls such as genetic background and home environment (diet, temperature and lighting) that are standard in biomedical laboratory research. Nonetheless, in adult humans, a 3-month period of CR impr...

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Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 88%

Section: Cr and Autophagymentioning

confidence: 99%

Section: Cr and Mitochondrial Healthmentioning

confidence: 99%

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Less is more: Caloric regulation of neurogenesis and adult brain function

Morgan

Andrews

Davies

2017

J Neuroendocrinology

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“…In addition, several studies have identified changes with age in signaling pathways (i.e. mTOR, SIRT, FOXO) that could contribute to reduced induction of autophagy and autophagosome formation (Bitto et al., 2014; Park et al., 2016; Perluigi, Di Domenico & Butterfield, 2015; Schiavi & Ventura, 2014). Future analysis will be required to explore the molecular requirements that determine the recruitment of motor proteins to AVs and LYS and the potential impact in this process of age‐associated changes in these signaling routes.…”

Section: Discussionmentioning

confidence: 99%

Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging

et al. 2018

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SummaryInability to preserve proteostasis with age contributes to the gradual loss of function that characterizes old organisms. Defective autophagy, a component of the proteostasis network for delivery and degradation of intracellular materials in lysosomes, has been described in multiple old organisms, while a robust autophagy response has been linked to longevity. The molecular mechanisms responsible for defective autophagic function with age remain, for the most part, poorly characterized. In this work, we have identified differences between young and old cells in the intracellular trafficking of the vesicular compartments that participate in autophagy. Failure to reposition autophagosomes and lysosomes toward the perinuclear region with age reduces the efficiency of their fusion and the subsequent degradation of the sequestered cargo. Hepatocytes from old mice display lower association of two microtubule‐based minus‐end‐directed motor proteins, the well‐characterized dynein, and the less‐studied KIFC3, with autophagosomes and lysosomes, respectively. Using genetic approaches to mimic the lower levels of KIFC3 observed in old cells, we confirmed that reduced content of this motor protein in fibroblasts leads to failed lysosomal repositioning and diminished autophagic flux. Our study connects defects in intracellular trafficking with insufficient autophagy in old organisms and identifies motor proteins as a novel target for future interventions aiming at correcting autophagic activity with anti‐aging purposes.

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“…Spleens were collected from aged mice in the control and metformin‐treated groups under aseptic conditions. Mouse splenocyte proliferation assay was performed as previously described . Splenocyte suspension (2×10 5 cells/mL) was placed into 96‐well plates (200 μL/well) and cultured at 37°C for 48 hour in a humid atmosphere containing 5% CO 2 in the presence of interleukin 2 (IL‐2) and lipopolysaccharides (LPS).…”

Section: Methodsmentioning

confidence: 99%

Metformin alleviates ageing cellular phenotypes in Hutchinson–Gilford progeria syndrome dermal fibroblasts

Park

Shin

2017

Experimental Dermatology

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Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and ageing prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature ageing and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients. Metformin treatment partially restored normal nuclear phenotypes, delayed senescence, activated the phosphorylation of AMP-activated protein kinase and decreased reactive oxygen species formation in HGPS dermal fibroblasts. Interestingly, metformin reduced the number of phosphorylated histone variant H2AX-positive DNA damage foci and suppressed progerin protein expression, compared to the control. Furthermore, metformin-supplemented aged mice showed higher splenocyte proliferation and mRNA expression of the antioxidant enzyme, superoxide dismutase 2 than the control mice. Collectively, our results show that metformin treatment alleviates the nuclear defects and premature ageing phenotypes in HGPS fibroblasts. Thus, metformin can be considered a promising therapeutic approach for life extension in HGPS.

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Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway

Cited by 27 publications

References 41 publications

Less is more: Caloric regulation of neurogenesis and adult brain function

Less is more: Caloric regulation of neurogenesis and adult brain function

Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging

Metformin alleviates ageing cellular phenotypes in Hutchinson–Gilford progeria syndrome dermal fibroblasts

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