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Aging Cell

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https://www.readbyqxmd.com/read/29214707/movement-decline-across-lifespan-of-caenorhabditis-elegans-mutants-in-the-insulin-insulin-like-signaling-pathway
#1
Breanne L Newell Stamper, James R Cypser, Katerina Kechris, David Alan Kitzenberg, Patricia M Tedesco, Thomas E Johnson
Research in aging biology has identified several pathways that are molecularly conserved across species that extend lifespan when mutated. The insulin/insulin-like signaling (IIS) pathway is one of the most widely studied of these. It has been assumed that extending lifespan also extends healthspan (the period of life with minimal functional loss). However, data supporting this assumption conflict and recent evidence suggest that life extension may, in and of itself, extend the frail period. In this study, we use Caenorhabditis elegans to further probe the link between lifespan and healthspan...
December 7, 2017: Aging Cell
https://www.readbyqxmd.com/read/29210174/autophagy-controls-mesenchymal-stem-cell-properties-and-senescence-during-bone-aging
#2
Yang Ma, Meng Qi, Ying An, Liqiang Zhang, Rui Yang, Daniel H Doro, Wenjia Liu, Yan Jin
Bone marrow-derived mesenchymal stem cells (BMMSCs) exhibit degenerative changes, including imbalanced differentiation and reduced proliferation during aging, that contribute to age-related bone loss. We demonstrate here that autophagy is significantly reduced in aged BMMSCs compared with young BMMSCs. The autophagy inhibitor 3-methyladenine (3-MA) could turn young BMMSCs into a relatively aged state by reducing their osteogenic differentiation and proliferation capacity and enhancing their adipogenic differentiation capacity...
December 6, 2017: Aging Cell
https://www.readbyqxmd.com/read/29210183/young-plasma-reverses-age-dependent-alterations-in-hepatic-function-through-the-restoration-of-autophagy
#3
Anding Liu, Enshuang Guo, Jiankun Yang, Yan Yang, Shenpei Liu, Xiaojing Jiang, Qi Hu, Olaf Dirsch, Uta Dahmen, Cuntai Zhang, David A Gewirtz, Haoshu Fang
Recent studies showing the therapeutic effect of young blood on aging-associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging-associated organ injuries, this study was designed to determine the effect of young blood on aging-induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3-methyladenine or wortmannin was used to inhibit young blood-induced autophagy...
December 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/29178390/foxo-protects-against-age-progressive-axonal-degeneration
#4
Inah Hwang, Hwanhee Oh, Evan Santo, Do-Yeon Kim, John W Chen, Roderick T Bronson, Jason W Locasale, Yoonmi Na, Jaclyn Lee, Stewart Reed, Miklos Toth, Wai H Yu, Florian L Muller, Jihye Paik
Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age-progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system-specific deletion of Foxo transcription factors in mice accelerates aging-related axonal tract degeneration, which is followed by motor dysfunction...
November 26, 2017: Aging Cell
https://www.readbyqxmd.com/read/29168299/17%C3%AE-estradiol-acts-through-hypothalamic-pro-opiomelanocortin-expressing-neurons-to-reduce-feeding-behavior
#5
Frederik J Steyn, Shyuan T Ngo, Vicky Ping Chen, Lora C Bailey-Downs, Teresa Y Xie, Martin Ghadami, Stephen Brimijoin, Willard M Freeman, Marcelo Rubinstein, Malcolm J Low, Michael B Stout
Weight loss is an effective intervention for diminishing disease burden in obese older adults. Pharmacological interventions that reduce food intake and thereby promote weight loss may offer effective strategies to reduce age-related disease. We previously reported that 17α-estradiol (17α-E2) administration elicits beneficial effects on metabolism and inflammation in old male mice. These observations were associated with reduced calorie intake. Here, we demonstrate that 17α-E2 acts through pro-opiomelanocortin (Pomc) expression in the arcuate nucleus (ARC) to reduce food intake and body mass in mouse models of obesity...
November 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/29168286/comparative-proteomic-profiling-reveals-a-role-for-cisd2-in-skeletal-muscle-aging
#6
Yi-Long Huang, Zhao-Qing Shen, Chia-Yu Wu, Yuan-Chi Teng, Chen-Chung Liao, Cheng-Heng Kao, Liang-Kung Chen, Chao-Hsiung Lin, Ting-Fen Tsai
Skeletal muscle has emerged as one of the most important tissues involved in regulating systemic metabolism. The gastrocnemius is a powerful skeletal muscle composed of predominantly glycolytic fast-twitch fibers that are preferentially lost among old age. This decrease in gastrocnemius muscle mass is remarkable during aging; however, the underlying molecular mechanism is not fully understood. Strikingly, there is a ~70% decrease in Cisd2 protein, a key regulator of lifespan in mice and the disease gene for Wolfram syndrome 2 in humans, within the gastrocnemius after middle age among mice...
November 23, 2017: Aging Cell
https://www.readbyqxmd.com/read/29166700/dlp1-dependent-mitochondrial-fragmentation-and-redistribution-mediate-prion-associated-mitochondrial-dysfunction-and-neuronal-death
#7
Chaosi Li, Di Wang, Wei Wu, Wei Yang, Syed Zahid Ali Shah, Ying Zhao, Yuhan Duan, Lu Wang, Xiangmei Zhou, Deming Zhao, Lifeng Yang
Mitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin-like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP(106-126) in vitro as well as in prion strain-infected hamster brain in vivo...
November 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/29143441/cellular-aging-dynamics-after-acute-malaria-infection-a-12-month-longitudinal-study
#8
Muhammad Asghar, Victor Yman, Manijeh Vafa Homann, Klara Sondén, Ulf Hammar, Dennis Hasselquist, Anna Färnert
Accelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real-time quantitative PCR, while telomerase activity and CDKN2A expression were measured by reverse transcriptase (RT)-qPCR...
November 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/29130578/sirt3-deregulation-is-linked-to-mitochondrial-dysfunction-in-alzheimer-s-disease
#9
Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E Alvarez, Ann C McKee, Soo-Jong Um, Manwook Hur, Inhee Mook-Jung, Neil W Kowall, Hoon Ryu
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD-dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD...
November 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/29120091/running-wheel-activity-delays-mitochondrial-respiratory-flux-decline-in-aging-mouse-muscle-via-a-post-transcriptional-mechanism
#10
Sarah Stolle, Jolita Ciapaite, Aaffien C Reijne, Alzbeta Talarovicova, Justina C Wolters, Raúl Aguirre-Gamboa, Pieter van der Vlies, Kim de Lange, Pieter B Neerincx, Gerben van der Vries, Patrick Deelen, Morris A Swertz, Yang Li, Rainer Bischoff, Hjalmar P Permentier, Peter L Horvatovitch, Albert K Groen, Gertjan van Dijk, Dirk-Jan Reijngoud, Barbara M Bakker
Loss of mitochondrial respiratory flux is a hallmark of skeletal muscle aging, contributing to a progressive decline of muscle strength. Endurance exercise alleviates the decrease in respiratory flux, both in humans and in rodents. Here, we dissect the underlying mechanism of mitochondrial flux decline by integrated analysis of the molecular network. Mice were given a lifelong ad libitum low-fat or high-fat sucrose diet and were further divided into sedentary and running-wheel groups. At 6, 12, 18 and 24 months, muscle weight, triglyceride content and mitochondrial respiratory flux were analysed...
November 9, 2017: Aging Cell
https://www.readbyqxmd.com/read/29119686/ketone-body-3-hydroxybutyrate-mimics-calorie-restriction-via-the-nrf2-activator-fumarate-in-the-retina
#11
Yusuke Izuta, Toshihiro Imada, Ryuji Hisamura, Erina Oonishi, Shigeru Nakamura, Emi Inagaki, Masataka Ito, Tomoyoshi Soga, Kazuo Tsubota
Calorie restriction (CR) being the most robust dietary intervention provides various health benefits. D-3-hydroxybutyrate (3HB), a major physiological ketone, has been proposed as an important endogenous molecule for CR. To investigate the role of 3HB in CR, we investigated potential shared mechanisms underlying increased retinal 3HB induced by CR and exogenously applied 3HB without CR to protect against ischemic retinal degeneration. The repeated elevation of retinal 3HB, with or without CR, suppressed retinal degeneration...
November 9, 2017: Aging Cell
https://www.readbyqxmd.com/read/29106033/brain-5-lipoxygenase-over-expression-worsens-memory-synaptic-integrity-and-tau-pathology-in-the-p301s-mice
#12
Alana N Vagnozzi, Phillip F Giannopoulos, Domenico Praticò
Progressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies. Data from human and animal models of these diseases have shown that neuroinflammation often accompanies their pathogenesis. The 5-lipoxygenase (5LO) is an enzyme widely expressed in the brain and a source of potent pro-inflammatory mediators, while its pharmacological inhibition modulates the phenotype of a tau transgenic mouse model, the htau mice...
November 4, 2017: Aging Cell
https://www.readbyqxmd.com/read/29094448/amyloid-beta-monomers-regulate-cyclic-adenosine-monophosphate-response-element-binding-protein-functions-by-activating-type-1-insulin-like-growth-factor-receptors-in-neuronal-cells
#13
Stefania Zimbone, Irene Monaco, Fiorenza Gianì, Giuseppe Pandini, Agata G Copani, Maria Laura Giuffrida, Enrico Rizzarelli
Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β-amyloid (Aβ), and neuronal loss. The self-association of Aβ monomers into soluble oligomers seems to be crucial for the development of neurotoxicity (J. Neurochem., 00, 2007 and 1172). Aβ oligomers have been suggested to compromise neuronal functions in AD by reducing the expression levels of the CREB target gene and brain-derived neurotrophic factor (BDNF) (J. Neurosci...
November 1, 2017: Aging Cell
https://www.readbyqxmd.com/read/29067790/sirt2-bubr1-acetylation-pathway-mediates-the-effects-of-advanced-maternal-age-on-oocyte-quality
#14
Danhong Qiu, Xiaojing Hou, Longsen Han, Xiaoyan Li, Juan Ge, Qiang Wang
The level of Sirt2 protein is reduced in oocytes from aged mice, while exogenous expression of Sirt2 could ameliorate the maternal age-associated meiotic defects. To date, the underlying mechanism remains unclear. Here, we confirmed that specific depletion of Sirt2 disrupts maturational progression and spindle/chromosome organization in mouse oocytes, with compromised kinetochore-microtubule attachments. Candidate screening revealed that acetylation state of lysine 243 on BubR1 (BubR1-K243, an integral part of the spindle assembly checkpoint complex) functions during oocyte meiosis, and acetylation-mimetic mutant BubR1-K243Q results in the very similar phenotypes as Sirt2-knockdown oocytes...
October 25, 2017: Aging Cell
https://www.readbyqxmd.com/read/29067788/pgc-1%C3%AE-affects-aging-related-changes-in-muscle-and-motor-function-by-modulating-specific-exercise-mediated-changes-in-old-mice
#15
Jonathan F Gill, Gesa Santos, Svenia Schnyder, Christoph Handschin
The age-related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age-associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise training in old age is sufficient to affect muscle and motor function. Moreover, as muscle peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key regulatory hub in endurance exercise adaptation with decreased expression in old muscle, we studied the involvement of PGC-1α in the therapeutic effect of exercise in aging...
October 25, 2017: Aging Cell
https://www.readbyqxmd.com/read/29047204/influence-of-cell-distribution-and-diabetes-status-on-the-association-between-mitochondrial-dna-copy-number-and-aging-phenotypes-in-the-inchianti-study
#16
Ann Zenobia Moore, Jun Ding, Marcus A Tuke, Andrew R Wood, Stefania Bandinelli, Timothy M Frayling, Luigi Ferrucci
Mitochondrial DNA copy number (mtDNA-CN) estimated in whole blood is a novel marker of mitochondrial mass and function that can be used in large population-based studies. Analyses that attempt to relate mtDNA-CN to specific aging phenotypes may be confounded by differences in the distribution of blood cell types across samples. Also, low or high mtDNA-CN may have a different meaning given the presence of diseases associated with mitochondrial damage. We evaluated the impact of blood cell type distribution and diabetes status on the association between mtDNA-CN and aging phenotypes, namely chronologic age, interleukin-6, hemoglobin, and all-cause mortality, among 672 participants of the InCHIANTI study...
October 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/29047229/enhanced-inflammation-and-attenuated-tumor-suppressor-pathways-are-associated-with-oncogene-induced-lung-tumors-in-aged-mice
#17
Neha Parikh, Ryan L Shuck, Mihai Gagea, Lanlan Shen, Lawrence A Donehower
Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic Kras(G12D) was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activation of Kras(G12D) in old mice resulted in shorter survival and development of higher-grade lung tumors. Six weeks after Kras(G12D) activation, old lung tissues contained higher numbers of adenomas than their young tissue counterparts...
October 18, 2017: Aging Cell
https://www.readbyqxmd.com/read/29045001/anti-inflammaging-effects-of-human-alpha-1-antitrypsin
#18
Ye Yuan, Benedetto DiCiaccio, Ying Li, Ahmed S Elshikha, Denis Titov, Brian Brenner, Lee Seifer, Hope Pan, Nurdina Karic, Mohammad A Akbar, Yuanqing Lu, Sihong Song, Lei Zhou
Inflammaging plays an important role in most age-related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha-1 antitrypsin (hAAT) has immune-regulatory, anti-inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti-inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT...
October 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/29044988/age-associated-microrna-expression-in-human-peripheral-blood-is-associated-with-all-cause-mortality-and-age-related-traits
#19
Tianxiao Huan, George Chen, Chunyu Liu, Anindya Bhattacharya, Jian Rong, Brian H Chen, Sudha Seshadri, Kahraman Tanriverdi, Jane E Freedman, Martin G Larson, Joanne M Murabito, Daniel Levy
Recent studies provide evidence of correlations of DNA methylation and expression of protein-coding genes with human aging. The relations of microRNA expression with age and age-related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole-blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10(-4) (Bonferroni-corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age-associated mRNA expression possibly driven by age-associated microRNAs in pathways that involve RNA processing, translation, and immune function...
October 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/29024417/human-cd8-emra-t-cells-display-a-senescence-associated-secretory-phenotype-regulated-by-p38-mapk
#20
Lauren A Callender, Elizabeth C Carroll, Robert W J Beal, Emma S Chambers, Sussan Nourshargh, Arne N Akbar, Sian M Henson
Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP). We show here that primary human senescent CD8(+) T cells also display a SASP comprising chemokines, cytokines and extracellular matrix remodelling proteases that are unique to this subset and contribute to age-associated inflammation. We found the CD8(+) CD45RA(+) CD27(-) EMRA subset to be the most heterogeneous, with a population aligning with the naïve T cells and another with a closer association to the effector memory subset...
October 12, 2017: Aging Cell
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