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AMPK Aging

Stanley Dumeus, Marthandam Asokan Shibu, Wan-Teng Lin, Ming-Fu Wang, Chao-Hung Lai, Chia-Yao Shen, Yueh-Min Lin, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
BACKGROUND/AIMS: High-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) poses therapeutic challenges in elderly subjects. Due to lack of efficient drug therapy, plant-based bioactive peptides have been studied as alternative strategy in NAFLD and for less toxicity in elderly. To mimic fatty liver in aging conditions, researchers highly commended the genetically engineered strains SAMP8 (senescence-accelerated mice prone 8). However, there is a paucity of reports about the anti-steatosis effects of bioactive peptides against fatty liver development under a combined action of high-fat diet exposure and aging process...
August 9, 2018: Cellular Physiology and Biochemistry
Kai Kaarniranta, Jakub Kajdanek, Jan Morawiec, Elzbieta Pawlowska, Janusz Blasiak
PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator of many genes involved in energy management and mitochondrial biogenesis. PGC-1α expression is associated with cellular senescence, organismal aging, and many age-related diseases, including AMD (age-related macular degeneration), an important global issue concerning vision loss. We and others have developed a model of AMD pathogenesis, in which stress-induced senescence of retinal pigment epithelium (RPE) cells leads to AMD-related pathological changes...
August 7, 2018: International Journal of Molecular Sciences
Stephen A Stricker
Many marine invertebrates are capable of providing an abundant supply of oocytes that are fertilized external to the female body, thereby making these specimens well suited for studies of development. Along with intensively analyzed model systems belonging to such groups as echinoderms, tunicates, mollusks, and annelids, various lesser-studied taxa can undergo an external mode of fertilization. For example, nemertean worms constitute a relatively small phylum of marine protostome worms whose optically clear oocytes are easily collected and fertilized in the laboratory...
2018: Results and Problems in Cell Differentiation
Andrea Bednářová, Aleš Tomčala, Michaela Mochanová, Dalibor Kodrík, Natraj Krishnan
The impact of disruption of adipokinetic hormone (AKH) signaling was studied during aging in Drosophila in a sexually dimorphic manner. A mutant ( Akh 1 ) producing a non-functional AKH peptide was compared with isogenized wild-type controls ( w 1118 ), and Akh -rescue line where AKH was ectopically expressed in the mutant background ( EE-Akh ). Longevity, fecundity, and locomotor activity rhythms remained unaffected by lack of AKH signaling. While the strength of rhythms declined in general with age across all fly lines tested this was more so in case of Akh 1 flies...
2018: Frontiers in Physiology
Ji-Hye Kim, Jun Mi Lee, Jong-Hoon Kim, Kwang Rok Kim
Sirtuins, a family of NAD+ -dependent deacetylase enzymes, have been identified as mammalian homologs of yeast silent information regulator 2 (SIR2). Sirtuin 6 (SIRT6) plays important roles in cell homeostasis, DNA damage repair, cancer suppression, and aging. SIRT6 overexpression improves metabolic diseases, such as hypercholesterolemia, cholesterol-related disease, and type 2 diabetes via AMP-activated protein kinase (AMPK) activation. SIRT6 is abundant in the liver and is a crucial target for patients with liver steatosis...
August 2, 2018: Biochemical and Biophysical Research Communications
Jahahreeh Finley
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by an accelerated aging phenotype that typically leads to death via stroke or myocardial infarction at approximately 14.6 years of age. Most cases of HGPS have been linked to the extensive use of a cryptic splice donor site located in the LMNA gene due to a de novo mutation, generating a truncated and toxic protein known as progerin. Progerin accumulation in the nuclear membrane and within the nucleus distorts the nuclear architecture and negatively effects nuclear processes including DNA replication and repair, leading to accelerated cellular aging and premature senescence...
September 2018: Medical Hypotheses
Gina Cavaliere, Emanuela Viggiano, Giovanna Trinchese, Chiara De Filippo, Antonietta Messina, Vincenzo Monda, Anna Valenzano, Raffaele I Cincione, Christian Zammit, Fabiano Cimmino, Angela Catapano, Francesco Sessa, Giovanni Messina, Marcellino Monda, Marianna Crispino, Maria Pina Mollica
Scope: The hypothalamus is a key brain region involved in the control of feeding and energy expenditure. Hypothalamic inflammation and oxidative stress are landmarks of both obesity and aging processes, although the molecular mechanisms are still unknown. Therefore, with the aim to understand the neurobiological mechanisms of energy homeostasis during aging, we evaluate the effects of long feeding high-fat diet (HFD) in rats, at different age, on modulation of hypothalamic molecular pathway, oxidative stress, and inflammation...
2018: Frontiers in Physiology
James P White, Andrew N Billin, Milton E Campbell, Alan J Russell, Kim M Huffman, William E Kraus
Skeletal muscle stem cell (MuSC) function declines with age and contributes to impaired muscle regeneration in older individuals. Acting through AMPK/p27Kip1 , we have identified a pathway regulating the balance between autophagy, apoptosis, and senescence in aged MuSCs. While p27Kip1 is implicated in MuSC aging, its precise role and molecular mechanism have not been elucidated. Age-related MuSC dysfunction was associated with reduced autophagy, increased apoptosis, and hypophosphorylation of AMPK and its downstream target p27Kip1 ...
July 18, 2018: Stem Cell Reports
L-Y Chen, Y Wang, R Terkeltaub, R Liu-Bryan
OBJECTIVE: In osteoarthritis (OA), articular chondrocytes manifest mitochondrial damage, including mitochondrial DNA 4977-bp (mtDNA4977 ) deletion that impairs mitochondrial function. OA chondrocytes have decreased activity of AMPK, an energy biosensor that promotes mitochondrial biogenesis. Here, we tested if pharmacologic AMPK activation, via downstream activation of predominately mitochondrially localized sirtuin 3 (SIRT3), reverses existing decreases in mitochondrial DNA (mtDNA) integrity and function in human OA chondrocytes and limits mouse knee OA development...
July 20, 2018: Osteoarthritis and Cartilage
Hans M Dalton, Sean P Curran
Across organisms, manipulation of biosynthetic capacity arrests development early in life, but can increase health- and lifespan post-developmentally. Here we demonstrate that this developmental arrest is not sickness but rather a regulated survival program responding to reduced cellular performance. We inhibited protein synthesis by reducing ribosome biogenesis (rps-11/RPS11 RNAi), translation initiation (ifg-1/EIF3G mutation and egl-45/EIF3A RNAi), or ribosome progression (cycloheximide treatment), all of which result in a specific arrest at larval stage 2 of C...
July 2018: PLoS Genetics
Sooho Lee, Nhu Huynh Le, Dongchul Kang
Oxidative stress plays an important role in the pathogenesis of aging-related osteoporosis through the increased bone resorption or reduced bone formation. Melatonin, which can exert beneficial actions through antioxidant, anti-inflammatory, and bone-preserving effects, shows promise in preventing oxidative stress-inhibited osteogenesis. However, specific mechanisms by which melatonin rescues oxidative stress-inhibited osteogenesis of human mesenchymal stem cells (MSCs) have not been fully elucidated yet. We therefore investigated whether activation of AMPK by melatonin regulates the antagonistic crosstalk between oxidative stress and osteogenic differentiation in human MSCs...
2018: International Journal of Medical Sciences
Katherine E Bathgate, James R Bagley, Edward Jo, Robert J Talmadge, Irene S Tobias, Lee E Brown, Jared W Coburn, Jose A Arevalo, Nancy L Segal, Andrew J Galpin
INTRODUCTION: Physical health and function depend upon both genetic inheritance and environmental factors (e.g., exercise training). PURPOSE: To enhance the understanding of heritability/adaptability, we explored the skeletal muscle health and physiological performance of monozygotic (MZ) twins with > 30 years of chronic endurance training vs. no specific/consistent exercise. METHODS: One pair of male MZ twins (age = 52 years; Trained Twin, TT; Untrained Twin, UT) underwent analyses of: (1) anthropometric characteristics and blood profiles, (2) markers of cardiovascular and pulmonary health, and (3) skeletal muscle size, strength, and power and molecular markers of muscle health...
July 14, 2018: European Journal of Applied Physiology
Rongfeng Yang, Wu Fang, Jiawen Liang, Chao Lin, Shaoyun Wu, Shaodi Yan, Chengheng Hu, Xiao Ke
Introduction: Previous studies have shown that endothelial cell senescence is involved in cardiovascular diseases such as cardiac fibrosis, atherosclerosis and heart failure. Accumulating evidence indicates that apelin exerts protective effects on ageing-related endothelial dysfunction. In this study, we aim to investigate the role of the apelin/APJ axis in angiotensin II (AngII)-induced endothelium senescence and its associated mechanisms. Material and methods: Senescence-related β-gal activity assay and western blot were used to evaluate human umbilical vein endothelial cell (HUVEC) senescence...
June 2018: Archives of Medical Science: AMS
Oliver Baretella, Aimin Xu, Paul M Vanhoutte
BACKGROUND: Aging, obesity, and diabetes favor vascular dysfunction. Endothelial activation of adenosine monophosphate-activated protein kinase (AMPK) has protective effects in diabetes. METHODS: Mice with constitutive endothelial activation of AMPK (CA-AMPK) were given a high fat diet to induce obesity or kept on standard chow as lean controls for up to 2 years. A subset of obese animals was changed to standard chow after 30 weeks of high fat feeding. En-dothelium-dependent and endothelium-independent responses were examined by isometric tension recording...
July 11, 2018: Journal of Vascular Research
Daisuke Tanokashira, Eiko Kurata, Wataru Fukuokaya, Kenshiro Kawabe, Mana Kashiwada, Hideyuki Takeuchi, Masamitsu Nakazato, Akiko Taguchi
Age-related reduction in adult hippocampal neurogenesis is correlated with cognitive impairment. Diabetes is a chronic systemic disease that negatively affects adult neural stem cells and memory functions in the hippocampus. Despite growing concern regarding the potential role of diabetic drugs in neural abnormalities, their effects on progressive deterioration of neurogenesis and cognitive functions remain unknown. Here, we show that the combination of aging and diabetes in mice causes a marked decrease in hippocampal neurogenesis along with memory impairment and elevated neuroinflammation...
July 2018: FEBS Open Bio
Jason Tallis, Rob S James, Frank Seebacher
Obesity can cause a decline in contractile function of skeletal muscle, thereby reducing mobility and promoting obesity-associated health risks. We reviewed the literature to establish the current state-of-knowledge of how obesity affects skeletal muscle contraction and relaxation. At a cellular level, the dominant effects of obesity are disrupted calcium signalling and 5'-adenosine monophosphate-activated protein kinase (AMPK) activity. As a result, there is a shift from slow to fast muscle fibre types. Decreased AMPK activity promotes the class II histone deacetylase (HDAC)-mediated inhibition of the myocyte enhancer factor 2 (MEF2)...
July 6, 2018: Journal of Experimental Biology
Yu Inata, Giovanna Piraino, Paul W Hake, Michael O'Connor, Patrick Lahni, Vivian Wolfe, Christine Schulte, Victoria Moore, Jeanne M James, Basilia Zingarelli
Age represents a major risk factor of multiple organ failure, including cardiac dysfunction, in patients with sepsis. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis, which controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ co-activator-α and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation contributes to age-dependent cardiac injury in young (2-3 months) and mature adult (11-13 months) male mice subjected to sepsis by cecal ligation and puncture, and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords cardioprotective effects...
July 6, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Richard A Perry, Lemuel A Brown, Wesley S Haynie, Jacob L Brown, Megan E Rosa-Caldwell, David E Lee, Nicholas P Greene, Tyrone A Washington
Sarcopenic obesity (SO) is the comorbidity of age-related muscle wasting and obesity. SO increases the risk of heart disease, but little is known about the cellular signaling in cardiac muscle of SO individuals. AIM: The purpose of this study was to identify key cellular signaling alterations in cardiac muscle of sarcopenic obese mice. METHODS: Thirty-two, male C57BL/6J mice were randomly divided into lean and high-fat fed groups and raised to 3-4 months (young) or 20-22 months (aged) of age...
June 26, 2018: Experimental Gerontology
Rubén Corpas, Christian Griñán-Ferré, Eduard Rodríguez-Farré, Mercè Pallàs, Coral Sanfeliu
Resveratrol is a natural compound that mimics the antioxidant and antiaging effects of caloric restriction, mainly mediated through SIRT1, a deacetylase that induces longevity and neuroprotection. We aimed to analyze the effects of resveratrol on the brain status of control non-transgenic (NoTg) and AD transgenic (3xTg-AD) mice to discern the mechanisms involved in a potential inducement of resilience against age-related neurodegeneration and Alzheimer's disease (AD). Mice were fed with a diet supplemented with 100 mg/kg of resveratrol from 2 months of age during 10 months...
June 13, 2018: Molecular Neurobiology
Yilin Shen, Bin Ye, Penghui Chen, Quan Wang, Cui Fan, Yilai Shu, Mingliang Xiang
The incidences of presbycusis and dementia are high among geriatric diseases. Presbycusis is the general term applied to age-related hearing loss and can be caused by many risk factors, such as noise exposure, smoking, medication, hypertension, family history, and other factors. Mutation of mitochondrial DNA in hair cells, spiral ganglion cells, and stria vascularis cells of the cochlea is the basic mechanism of presbycusis. Dementia is a clinical syndrome that includes the decline of cognitive and conscious states and is caused by many neurodegenerative diseases, of which Alzheimer's disease (AD) is the most common...
2018: Frontiers in Neuroscience
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