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AMPK Aging

Fei Wang, Yanchang Shang, Rong Zhang, Xiangyang Gao, Qiang Zeng
Sirtuin 1 (SIRT1) is an NAD+‑dependent protein deacetylase that is involved in cell differentiation, aging, apoptosis, physiological rhythms, metabolic regulation, oxidative stress and numerous other important biological processes. In the present study, the ability of a sirtuin‑1 (SIRT1) agonist, SRT1720, to reduce cognitive decline in type 2 diabetes mellitus (T2DM) was investigated. Streptozotocin‑induced male Sprague‑Dawley rats were used to establish a T2DM model and the protective effect of SRT1720 and its underlying mechanisms were investigated...
November 27, 2018: Molecular Medicine Reports
Danuta Z Loesch, Nicholas Trost, Minh Q Bui, Eleanor Hammersley, Sui T Lay, Sarah J Annesley, Oana Sanislav, Claire Y Allan, Flora Tassone, Zhi-Ping Chen, Kevin R W Ngoei, Bruce E Kemp, David Francis, Paul R Fisher, Elsdon Storey
The fragile X premutation (PM) allele contains a CGG expansion of 55-200 repeats in the FMR1 gene's promoter. Male PM carriers have an elevated risk of developing neurological and psychiatric changes, including an approximately 50% risk of the fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to assess the relationships of regional white matter hyperintensities ( wmhs ) semi-quantitative scores, clinical status, motor (UPDRS, ICARS, Tremor) scales, and cognitive impairments, with FMR1 -specific genetic changes, in a sample of 32 unselected male PM carriers aged 39-81 years...
2018: Frontiers in Genetics
Jianlong Gao, Rui Xiong, Dan Xiong, Wenxing Zhao, Sheng Zhang, Tao Yin, Xinhua Zhang, Guozhen Jiang, Zhengyu Yin
BACKGROUND The development and progression of hepatocellular carcinoma (HCC) are associated with obesity and hepatosteatosis. AMP-activated protein kinase (AMPK) regulates metabolic homeostasis. This study aimed to investigate the effects of treatment with the adenosine monophosphate (AMP) analog, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on hepatosteatosis in a mouse model fed a high-fat diet (HFD), and on hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in the HFD mouse model...
November 26, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Alexander Panossian, Ean-Jeong Seo, Thomas Efferth
INTRODUCTION: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood...
November 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Haiming Jin, Zengjie Zhang, Chengui Wang, Qian Tang, Jianle Wang, Xueqin Bai, Qingqing Wang, Majid Nisar, Naifeng Tian, Quan Wang, Cong Mao, Xiaolei Zhang, Xiangyang Wang
Wound healing is delayed in diabetic patients. Increased apoptosis and endothelial progenitor cell (EPC) dysfunction are implicated in delayed diabetic wound healing. Melatonin, a major secretory product of the pineal gland, promotes diabetic wound healing; however, its mechanism of action remains unclear. Here, EPCs were isolated from the bone marrow of mice. Treatment of EPCs with melatonin alleviated advanced glycation end product (AGE)-induced apoptosis and cellular dysfunction. We further examined autophagy flux after melatonin treatment and found increased light chain 3 (LC3) and p62 protein levels in AGE-treated EPCs...
November 21, 2018: Experimental & Molecular Medicine
Amir Hafidz Md Mokhtar, Ifrah Alam Malik, Noor Azean Anis Abd Aziz, Fayez A Almabhouh, Damayanthi Durairajanayagam, Harbindar Jeet Singh
This study examined the effects of PI3K and AMPK signalling pathway inhibitors on leptin-induced adverse effects on rat spermatozoa. Sprague-Dawley rats, aged 14-16 weeks, were randomised into control, leptin-, leptin + dorsomorphin (AMPK inhibitor)-, and leptin+LY294002 (PI3K inhibitor)-treated groups with six rats per group. Leptin was given once daily for 14 days via the intraperitoneal (i.p.) route at a dose of 60 ug kg-1 body weight. Rats in the leptin and inhibitor-treated groups received concurrently either dorsomorphin (5 mg kg-1  day-1 ) or LY294002 (1...
November 19, 2018: Andrologia
Ravi Kumar, Anamika Sharma, Amita Kumari, Ashu Gulati, Yogendra Padwad, Rohit Sharma
The phytochemical epigallocatechin gallate (EGCG) has been reported to alleviate age-associated immune disorders and organ dysfunction. However, information regarding the mechanistic role of EGCG in the suppression of cellular senescence is limited. The present study thus assessed the effects and underlying mechanisms of EGCG in the inhibition of senescence as well as its potential to selectively eliminate senescent cells (senolytics) using 3T3-L1 preadipocytes. Premature senescence was established in cells by repeated exposure of H2 O2 at a sub-lethal concentration (150 μM)...
November 19, 2018: Biogerontology
Huaping Zhang, Xiaorong Yang, Xuefen Pang, Zhenxiang Zhao, Haixia Yu, Hui Zhou
The anti-senescence activity of genistein is associated with inducing autophagy; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein (1000 nM) for 30 min and then exposed to ox-LDL (50 mg/L) for another 12 h. The study found that genistein inhibited the ox-LDL-induced senescence (reducing the levels of P16 and P21 protein, and the activity of SA-β-gal); meanwhile, the effect of genistein was bound up with enhancing autophagic flux (increasing LC3-II, and decreasing the level of P62, p-mTOR and p-P70S6K)...
November 16, 2018: Molecular and Cellular Biochemistry
Mohammad Harun-Or-Rashid, Denise M Inman
BACKGROUND: Glaucoma is a chronic degenerative disease for which inflammation is considered to play a pivotal role in the pathogenesis and progression. In this study, we examined the impact of a ketogenic diet on the inflammation evident in glaucoma as a follow-up to a recent set of experiments in which we determined that a ketogenic diet protected retinal ganglion cell structure and function. METHODS: Both sexes of DBA/2J (D2) mice were placed on a ketogenic diet (keto) or standard rodent chow (untreated) for 8 weeks beginning at 9 months of age...
November 13, 2018: Journal of Neuroinflammation
Yi-Ping Wang, Qun-Ying Lei
Metabolite sensing is one of the most fundamental biological processes. During evolution, multilayered mechanisms developed to sense fluctuations in a wide spectrum of metabolites, including nutrients, to coordinate cellular metabolism and biological networks. To date, AMPK and mTOR signaling are among the best-understood metabolite-sensing and signaling pathways. Here, we propose a sensor-transducer-effector model to describe known mechanisms of metabolite sensing and signaling. We define a metabolite sensor by its specificity, dynamicity, and functionality...
2018: Signal Transduction and Targeted Therapy
Liting Hang, John Thundyil, Geraldine W Y Goh, Kah-Leong Lim
Parkinson's disease (PD) is a prevalent neurodegenerative movement disorder that is characterized pathologically by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) of the midbrain. Despite intensive research, the etiology of PD remains poorly understood. Interestingly, recent studies have implicated neuronal energy dysregulation as one of the key perpetrators of the disease. Supporting this, we have recently demonstrated that pharmacological or genetic activation of AMP kinase (AMPK), a master regulator of cellular energy homeostasis, rescues the pathological phenotypes of Drosophila models of PD...
November 8, 2018: Neuromolecular Medicine
Chia-Shan Wu, Qiong Wei, Hongying Wang, Da Mi Kim, Miriam Balderas, Guoyao Wu, John Lawler, Stephen Safe, Shaodong Guo, Sridevi Devaraj, Zheng Chen, Yuxiang Sun
Sarcopenia is the aging-associated progressive loss of skeletal muscle, however the pathogenic mechanism of sarcopenia is not clear. The orexigenic hormone ghrelin stimulates growth hormone secretion, increases food intake, and promotes adiposity. Here we showed that fasting-induced muscle loss was exacerbated in old ghrelin-null (Ghrl-/-) mice, exhibiting decreased expression of myogenic regulator MyoD and increased expression of protein degradation marker MuRF1, as well as altered mitochondrial function. Moreover, acylated ghrelin (AG) and unacylated ghrelin (UAG) treatments significantly increased mitochondrial respiration capacity in muscle C2C12 cells...
November 8, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Fane F K Mensah, Christopher W Armstrong, Venkat Reddy, Amolak S Bansal, Saul Berkovitz, Maria J Leandro, Geraldine Cambridge
CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). Here, we investigated the relationship between CD24 expression and B cell maturation. In vitro stimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation)...
2018: Frontiers in Immunology
Jie Zhang, Caixia Wang, Haibo Shi, Danhong Wu, Weihai Ying
Cumulating evidence has indicated NAD+ deficiency as a common central pathological factor of multiple diseases and aging. NAD+ supplement is highly protective in various disease and aging models, while two key questions have remained unanswered: (1) Does extracellular NAD+ also produce its effects through its degradation product adenosine? (2) Does extracellular NAD+ produce the protective effects by affecting cells under pathological insults only, or by affecting both normal cell and the cells under pathological insults? Since extracellular NAD+ can be degraded into adenosine, and endogenous adenosine levels are in the nanomolar range under physiological conditions, extracellular NAD+ may produce its effects through its degradation into adenosine...
2018: Frontiers in Cellular Neuroscience
Jing Tian, Wenzhu Tang, Ming Xu, Chen Zhang, Pei Zhao, Tongtong Cao, Xiaoli Shan, Rong Lu, Wei Guo
BACKGROUND/AIMS: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. METHODS: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined...
2018: Cellular Physiology and Biochemistry
Anding Liu, Jiankun Yang, Qi Hu, Olaf Dirsch, Uta Dahmen, Cuntai Zhang, David A Gewirtz, Haoshu Fang, Jian Sun
Aging is often associated with a decreased autophagic activity that contributes to the high sensitivity of aged livers to ischemia reperfusion injury (IRI). Blood from young animals can positively affect aged animals. This study was designed to evaluate the effect of young plasma in a model of liver IRI in aged rats. Aged rats were treated with pooled plasma collected from young rats before ischemia. Administration of young plasma restored aging-induced suppression in hepatic autophagic activity and reduced liver IRI...
November 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xuan Li, Jia Liu, Haiyan Hu, Shaoxin Lu, Qingguo Lu, Nanhu Quan, Thomas Rousselle, Mulchand S Patel, Ji Li
Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), regulates substrate metabolism in the heart. AMP-activated protein kinase (AMPK) is an age-related energy sensor that protects the heart from ischemic injury. This study aims to investigate whether DCA can protect the heart from ischemic injury through the AMPK signaling pathway. Young (3-4 months) and aged (20-24 months) male C57BL/6J mice were subjected to ligation of the left anterior descending coronary artery (LAD) for an in vivo ischemic model...
October 29, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Eugene Chang, Dae-Hee Kim, Hyekyung Yang, Da Hyun Lee, Soo Han Bae, Cheol-Young Park
Previous studies have shown that the CB1 receptor antagonist reverses steatohepatitis and its related features of metabolic syndrome, such as obesity and type 2 diabetes. However, the beneficial effects of CB1 receptor blockade on hepatic steatosis and inflammation have not been investigated independently of its effects on body weight and glycemic control. At 32 weeks of age, OLETF rats were administered with rimonabant (10 mg·kg-1·day-1) by oral gavage for 6 weeks. No significant changes in body weight, OGTT, and serum glucose were observed in spite of rimonabant-decreased food intake...
2018: PloS One
Anthony J Donato, Daniel R Machin, Lisa A Lesniewski
Advancing age promotes cardiovascular disease (CVD), the leading cause of death in the United States and many developed nations. Two major age-related arterial phenotypes, large elastic artery stiffening and endothelial dysfunction, are independent predictors of future CVD diagnosis and likely are responsible for the development of CVD in older adults. Not limited to traditional CVD, these age-related changes in the vasculature also contribute to other age-related diseases that influence mammalian health span and potential life span...
September 14, 2018: Circulation Research
Hak Joo Lee, Olga Gonzalez, Edward J Dick, Andrew Donati, Denis Feliers, Choudhury Goutam Ghosh, Corinna Ross, Manjeri Venkatachalam, Suzette D Tardif, Balakuntalam S Kasinath
We evaluated whether the marmoset, a nonhuman primate, can serve as a good model to study aging related changes in the kidney by employing healthy young and aged marmosets of both sexes. Aging was associated with glomerulosclerosis, interstitial fibrosis and arteriolosclerosis in both sexes; correspondingly, the content of matrix proteins was increased. Functionally, aging resulted in an increase in urinary albumin and protein excretion. There was a robust correlation between markers of fibrosis and functional changes...
October 13, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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