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AMPK Aging

Xia Zhao, Zhiwen Zeng, Uma Gaur, Jiankang Fang, Tangming Peng, Shuai Li, Wenhua Zheng
Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H2 O2 -induced cell death...
February 19, 2019: Journal of Cellular Physiology
Timothy Nacarelli, Lena Lau, Takeshi Fukumoto, Joseph Zundell, Nail Fatkhutdinov, Shuai Wu, Katherine M Aird, Osamu Iwasaki, Andrew V Kossenkov, David Schultz, Ken-Ichi Noma, Joseph A Baur, Zachary Schug, Hsin-Yao Tang, David W Speicher, Gregory David, Rugang Zhang
Cellular senescence is a stable growth arrest that is implicated in tissue ageing and cancer. Senescent cells are characterized by an upregulation of proinflammatory cytokines, which is termed the senescence-associated secretory phenotype (SASP). NAD+ metabolism influences both tissue ageing and cancer. However, the role of NAD+ metabolism in regulating the SASP is poorly understood. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD+ salvage pathway, governs the proinflammatory SASP independent of senescence-associated growth arrest...
February 18, 2019: Nature Cell Biology
Wen-Jun Yan, Da-Bin Wang, Dong-Qing Ren, Ling-Kai Wang, Zhong-Yuan Hu, Ya-Bing Ma, Jin-Wen Huang, Shao-Li Ding
Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients who undergo surgery involving anesthesia. Its underlying mechanisms remain unclear. Autophagy plays an important role in the damage and repair of the nervous system and is associated with the development of POCD. Using a rat model, adenosine monophosphate-activated protein kinase α1 (AMPKα1), an important autophagy regulator, was found to be significantly downregulated in rats with POCD that was induced by sevoflurane anesthesia or by appendectomy...
February 18, 2019: Journal of Cellular Biochemistry
Thi Kim Quy Ha, Ha Thanh Tung Pham, Hyo Moon Cho, Van On Tran, Jun-Li Yang, Da-Woon Jung, Darren R Williams, Won Keun Oh
The aging population is growing rapidly around the world and there is also an increase in sarcopenia, which is characterized by decreased muscle mass, strength and function in the elderly population. AMP-activated protein kinase (AMPK) is an essential sensor and regulator of glucose, lipid and energy metabolism throughout the body. Previous studies have shown that AMPK pathway activation by regular exercise and appropriate dietary control have beneficial effects on skeletal muscle. In the process of searching for new AMPK activators from medicinal plants, we isolated and characterized eight new 12,23-dione dammarane triterpenoids (1-3 and 5-9), as well as one known gypentonoside A from Gynostemma longipes...
February 4, 2019: Scientific Reports
Seok Jeong Yoon, Chae Jin Lim, Hwa-Jee Chung, Joo-Hwan Kim, Yang Hoon Huh, Keedon Park, Sekyoo Jeong
Pollution-induced skin damage results in oxidative stress; cellular toxicity; inflammation; and, ultimately, premature skin aging. Previous studies suggest that the activation of autophagy can protect oxidation-induced cellular damage and aging-like changes in skin. In order to develop new anti-pollution ingredients, this study screened various kinds of natural extracts to measure their autophagy activation efficacy in cultured dermal fibroblast. The stimulation of autophagy flux by the selected extracts was further confirmed both by the expression of proteins associated with the autophagy signals and by electron microscope...
January 26, 2019: International Journal of Molecular Sciences
Christian Morsczeck
OBJECTIVE: This short review summarizes our current knowledge about dental stem cell aging and about possible targets for the regulation of cellular senescence. DESIGN: A literature search was performed using a combination of keywords, e.g., stem cells, replicative senescence, differentiation potential, dental pulp, dental follicle and periodontal ligament. RESULTS: Previous studies have shown that cellular senescence occurs while the proliferation of dental stem cells...
January 17, 2019: Archives of Oral Biology
Santie Li, Zhongxin Zhu, Mei Xue, Xinchu Yi, Jiaojiao Liang, Chao Niu, Gen Chen, Yingjie Shen, Hongping Zhang, Jiayong Zheng, Congcong Zhao, Yangzhi Liang, Weitao Cong, Yang Wang, Litai Jin
AIMS: This study investigated the mechanism through which fibroblast growth factor 21 (FGF21) protects against angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction. METHODS: Male silent information regulator 1 (SIRT1) flox/flox and cardiomyocyte-specific inducible SIRT1 knockout mice (SIRT1-iKO) were generated and treated with Ang II (1.1 mg/kg/day for 4 weeks) at the age of 8-12-week-old. FGF21 treatment [2.5 mg/kg/day for 4 weeks by intraperitoneal (i...
January 21, 2019: Biochimica et biophysica acta. Molecular basis of disease
Chu-Jen Kuo, Chi-Chen Huang, Szu-Yi Chou, Yu-Chun Lo, Tzu-Jen Kao, Nai-Kuei Huang, Connie Lin, Hsin-Chuan Lin, Hui-Ching Lin, Yi-Chao Lee
BACKGROUND: Curcumin is a polyphenol natural product of the plant Curcuma longa. Recent studies suggest that curcumin inhibit mTOR activity in vitro, which prompts us to investigate curcumin function as a new class of mTOR inhibitor suitable for tuberous sclerosis complex (TSC) treatment. PURPOSE: We aim to investigate the efficacy of curcumin in the treatment of TSC related manifestations in animal model. STUDY DESIGN: Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice...
September 20, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ching-Chou Tsai, Mao-Meng Tiao, Jiunn-Ming Sheen, Li-Tung Huang, You-Lin Tain, I-Chun Lin, Yu-Ju Lin, Yun-Ju Lai, Chih-Cheng Chen, Kow-Aung Chang, Hong-Ren Yu
BACKGROUND: Prenatal dexamethasone treatment has been shown to enhance the susceptibility of offspring to postnatal high-fat (HF) diet-induced programmed obesity. We investigated the metabolic phenotypes, nutrient-sensing signal and circadian-clock genes in adipose tissue that are programmed by prenatal dexamethasone exposure and postnatal HF diet. METHODS: Male offspring of Sprague-Dawley rats were divided into four experimental groups: normal diet, prenatal dexamethasone exposure, postnatal HF diet, and prenatal dexamethasone plus postnatal HF diet...
January 18, 2019: Lipids in Health and Disease
A A Dalina, I E Kovaleva, A V Budanov
Sestrins belong to a family of evolutionary conserved proteins which are found in the majority of animal species. While invertebrate genomes contain only one sestrin gene, mammalian and other vertebrate genomes comprise three highly homologous genes that encode Sestrin 1, 2 and 3 proteins (Sesn1, Sesn2 and Sesn3). Sestrins are activated in response to a variety of stimuli and trigger metabolic shifts promoting cell survival under stress conditions. Although cellular stress within an organism is often caused by external stimuli it can be induced by excess of cytokines, chemokines, reactive oxygen species which are produced during aberrant metabolic or immune processes and are involved in regulation of cell physiological states including cell death...
November 2018: Molekuliarnaia Biologiia
Sang R Lee, Sun Woo Kwon, Young Ho Lee, Pelin Kaya, Jong Min Kim, Changhwan Ahn, Eui-Man Jung, Geun-Shik Lee, Beum-Soo An, Eui-Bae Jeung, Bae-Keun Park, Eui-Ju Hong
BACKGROUND: Women have a lower risk of hepatocellular carcinoma (HCC) than men, and the decreased possibility of HCC in women is thought to depend on estrogen levels. As a soybean-isoflavone product, genistein has estrogenic activity in various reproductive tissues, because it mimics 17β-estradiol and binds the estrogen receptor. Though genistein is a known liver cancer suppressor, its effects have not been studies in long-term experiment, where genistein is fed to a female animal model of HCC...
January 3, 2019: BMC Cancer
Lu Zhang, Zhenzhen Zhang, Jing Wang, Dongying Lv, Tianqi Zhu, Feng Wang, Xiuzhi Tian, Yujun Yao, Pengyun Ji, Guoshi Liu
Female fertility irreversibly declines with aging and this, is primarily associated with the decreased quality and quantity of oocytes. To evaluate whether a long-term of melatonin treatment would improve the fertility of aged mice, different concentrations of melatonin (10-3 , 10-5 , 10-7 M) were supplemented into drinking water. Melatonin treatments improved the litter sizes of mice at the age of 24 weeks. Mice treated with 10-5 M melatonin had the largest litter size among other concentrations. At this optimal concentration, melatonin not only significantly increased the total number of oocytes but also their quality, having more oocytes with normal morphology that could generate more blastocyst after in vitro fertilization in melatonin (10-5 M) treated group than that in the controls...
December 30, 2018: Journal of Pineal Research
Yan-Yan Hor, Cheong-Hwa Ooi, Boon-Yin Khoo, Sy-Bing Choi, Azman Seeni, Shaharum Shamsuddin, Chern-Ein Oon, Kee-Leong Ong, Woo-Sik Jeong, Min-Tze Liong
Aging is an inevitable and ubiquitous progress that affects all living organisms. A total of 18 strains of lactic acid bacteria (LAB) were evaluated on the activation of adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor mediating lifespan extension. The cell-free supernatant (CFS) of Lactobacillus fermentum DR9 (LF-DR9), Lactobacillus paracasei OFS 0291 (LP-0291), and Lactobacillus helveticus OFS 1515 (LH-1515) showed the highest activation of AMPK and was further evaluated...
December 28, 2018: Journal of Medicinal Food
Yanjun Li, Yanhong Xue, Xiaojun Xu, Guopeng Wang, Yiqun Liu, Hao Wu, Wenhui Li, Yueying Wang, Ziheng Chen, Weilin Zhang, Yushan Zhu, Wei Ji, Tao Xu, Lei Liu, Quan Chen
Both protein quality and mitochondrial quality are vital for the cellular activity, and impaired proteostasis and mitochondrial dysfunction are common etiologies of aging and age-related disorders. Here, we report that the mitochondrial outer membrane protein FUNDC1 interacts with the chaperone HSC70 to promote the mitochondrial translocation of unfolded cytosolic proteins for degradation by LONP1 or for formation of non-aggresomal mitochondrion-associated protein aggregates (MAPAs) upon proteasome inhibition in cultured human cells...
December 27, 2018: EMBO Journal
Buhui Liu, Yue Tu, Weiming He, Yinglu Liu, Wei Wu, Qijun Fang, Haitao Tang, Renmao Tang, Ziyue Wan, Wei Sun, Yigang Wan
The kidney is a typical organ undergoing age and injury. Hyperoside is reported to be useful for preventing aging induced by D-galactose (D-gal). However, therapeutic mechanisms remain unclear. We thereby aimed to verify whether hyperoside, compared to vitamin E (VE), could alleviate renal aging and injury by regulating autophagic activity and its related signaling pathways. In vivo , rats were administered with either hyperoside or VE after renal aging modeling induced by D-gal. Changes in renal aging and injury markers, autophagic activity and AMPK-ULK1 signaling pathway in the kidneys were analysed...
December 24, 2018: Aging
Li Liu, Ling Yao, Shang Wang, Zhiwei Chen, Tingli Han, Peng Ma, Lirong Jiang, Chunlin Yuan, Jinxiu Li, Dazhi Ke, Chunli Li, Johji Yamahara, Yuhao Li, Jianwei Wang
SCOPE: This study investigated the dual actions of 6-gingerol in stimulating both plasma adiponectin and muscular adiponectin receptor signalling in naturally ageing rats. METHODS AND RESULTS: Twenty-two-month-old male SD rats were treated with 6-gingerol (0.2 mg/kg, once daily) for 7 weeks. 6-Gingerol could attenuate age-associated high plasma triglyceride, glucose and insulin concentrations under fasting conditions as well as suppress the increase in the HOMA-IR index and inhibit the decrease of muscular p-Akt/Akt protein in ageing rats, which indicates an improvement of systemic and muscular insulin sensitivity...
December 21, 2018: Molecular Nutrition & Food Research
Laura Kitzmiller, John R Ledford, Paul W Hake, Michael O'Connor, Giovanna Piraino, Basilia Zingarelli
A serious consequence of sepsis is acute lung injury, whose severity is particularly impacted by the age of the patient. AMP-activated protein kinase (AMPK) is a crucial regulator of cellular metabolism, which controls mitochondrial biogenesis and autophagy. Here, we investigated the effect of pharmacological activation of AMPK with A769662 on lung injury by using a model that would preferably mimic the clinical condition of adult patients. Male C57BL/6 retired breeder mice (7-9 months old) were subjected to sepsis by cecal ligation and puncture (CLP)...
December 13, 2018: Shock
Yi-Fang Li, Shu-Hua Ouyang, Long-Fang Tu, Xi Wang, Wei-Lin Yuan, Guo-En Wang, Yan-Ping Wu, Wen-Jun Duan, Hong-Min Yu, Zhong-Ze Fang, Hiroshi Kurihara, Youwei Zhang, Rong-Rong He
Skin cells are vulnerable to oxidative stress-induced senescence, which may lead to abnormal aging or aging-related disorders. Therefore, strategies that can ameliorate oxidative stress-induced senescence are expected to protect skin from damage, holding the promise of treating skin diseases in the clinic. This study aims to investigate whether caffeine, a well-known purine alkaloid, is able to prevent skin from oxidative stress-induced senescence, and to explore the underlying molecular mechanisms. Methods : A free radical inducer 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) was used to induce oxidative stress and cellular senescence in both transformed skin cells and in normal human epidermal keratinocytes (NHEKs)...
2018: Theranostics
Saman Bahrambeigi, Bahman Yousefi, Mahdi Rahimi, Vahid Shafiei-Irannejad
The prevalence of diabetes mellitus especially type 2 diabetes mellitus is increasing all over the world. In addition to cardiomyopathy and nephropathy, diabetics are at higher risk of mortality and morbidity due to greater risk of bone fractures and skeletal abnormalities. Patients with diabetes mellitus have lower bone quality in comparison to their non-diabetic counterparts mainly because of hyperglycemia, toxic effects of advanced glycosylation end-products (AGEs) on bone tissue, and impaired bone microvascular system...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Mohamad-Reza Aghanoori, Darrell R Smith, Shiva Shariati-Ievari, Andrew Ajisebutu, Annee Nguyen, Fiona Desmond, Carlos H A Jesus, Xiajun Zhou, Nigel A Calcutt, Michel Aliani, Paul Fernyhough
OBJECTIVE: Diabetic sensorimotor polyneuropathy (DSPN) affects approximately half of diabetic patients leading to significant morbidity. There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes. We hypothesized that sub-optimal insulin-like growth factor 1 (IGF-1) signaling in diabetes drives loss of AMPK activity and mitochondrial function, both contributing to development of DSPN...
November 28, 2018: Molecular Metabolism
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