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Mechanisms of Ageing and Development

A Fagan-Murphy, L Hachoumi, M S Yeoman, B A Patel
Reactive oxygen and nitrogen species (ROS/RNS) have been widely implicated in the ageing process and various approaches exist for monitoring these species in biological tissues. These approaches at present are limited to monitoring either a single pro-oxidant species or total pro-oxidant levels and therefore provide limited insight into the range of pro-oxidant species and their relative proportions in the ageing process. We have utilised a sensor that allows us to simultaneously monitor hydrogen peroxide, peroxynitrite, nitric oxide and nitrite...
October 14, 2016: Mechanisms of Ageing and Development
Rijan Bajracharya, J William O Ballard
Dietary management plays a key role in the treatment of many diseases. However, no prospective studies have critically investigated the potential for dietary modification to delay the onset, or slow the progression, of Parkinson's Disease (PD). To study whether manipulating the Protein to Carbohydrate (P:C) ratio in the diet could affect the progression of PD, we compared Drosophila melanogaster parkin null mutants and their experimental controls fed with diets differing in their P:C ratio. We considered lifespan and feeding behaviors as well as motor and cellular functions on the 1:2 and 1:16 P:C diets...
October 6, 2016: Mechanisms of Ageing and Development
Clara Soria-Valles, Alejandro López-Soto, Fernando G Osorio, Carlos López-Otín
Genome instability is a hallmark of both cancer and aging processes. Beyond cell-autonomous responses, it is known that DNA damage also elicits systemic mechanisms aimed at favoring survival and damaged cells clearance. Among these mechanisms, immune activation and NF-κB-mediated inflammation play central roles in organismal control of DNA damage. We focus herein on the different experimental evidences that have allowed gaining mechanistic insight about this relationship. We also describe the functional consequences of defective immune function in cancer development and age-related alterations...
October 5, 2016: Mechanisms of Ageing and Development
Sulev Kõks, Soner Dogan, Bilge Guvenc Tuna, Herminia González-Navarro, Paul Potter, Roosmarijn E Vandenbroucke
Ageing is a process that gradually increases the organism's vulnerability to death. It affects different biological pathways, and the underlying cellular mechanisms are complex. In view of the growing disease burden of ageing populations, increasing efforts are being invested in understanding the pathways and mechanisms of ageing. We review some mouse models commonly used in studies on ageing, highlight the advantages and disadvantages of the different strategies, and discuss their relevance to disease susceptibility...
October 4, 2016: Mechanisms of Ageing and Development
Kalliopi Stratigi, Ourania Chatzidoukaki, George A Garinis
Nuclear architecture and the chromatin state affect most-if not all- DNA-dependent transactions, including the ability of cells to sense DNA lesions and restore damaged DNA back to its native form. Recent evidence points to functional links between DNA damage sensors, DNA repair mechanisms and the innate immune responses. The latter raises the question of how such seemingly disparate processes operate within the intrinsically complex nuclear landscape and the chromatin environment. Here, we discuss how DNA damage-induced immune responses operate within chromatin and the distinct sub-nuclear compartments highlighting their relevance to chronic inflammation...
October 1, 2016: Mechanisms of Ageing and Development
Inês Figueira, Adelaide Fernandes, Aleksandra Mladenovic, Andres Lopez-Contreras, Catarina M Henriques, Colin Selman, Elisabete Ferreiro, Efstathios S Gonos, José Luis Trejo, Juhi Misra, Lene Juel Rasmussen, Sara Xapelli, Timothy Ellam, Ilaria Bellantuono
Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity...
September 29, 2016: Mechanisms of Ageing and Development
Ashley B Williams, Björn Schumacher
The critical need for species preservation has driven the evolution of mechanisms that integrate stress signals from both exogenous and endogenous sources. Past research has been largely focused on cell-autonomous stress responses; however, recently their systemic outcomes within an organism and their implications at the ecological and species levels have emerged. Maintenance of species depends on the high fidelity transmission of the genome over infinite generations; thus, many pathways exist to monitor and restore the integrity of the genome and to coordinate DNA repair with other cellular processes, such as cell division and growth...
September 26, 2016: Mechanisms of Ageing and Development
Izabela Sadowska-Bartosz, Grzegorz Bartosz
Vast evidence supports the view that glycation of proteins is one of the main factors contributing to aging and is an important element of etiopathology of age-related diseases, especially type 2 diabetes mellitus, cataract and neurodegenerative diseases. Counteracting glycation can therefore be a means of increasing both the lifespan and healthspan. In this review, accumulation of glycation products during aging is presented, pathophysiological effects of glycation are discussed and ways of attenuation of the effects of glycation are described, concentrating on prevention of glycation...
September 23, 2016: Mechanisms of Ageing and Development
Haibo Wang, Prakash Dharmalingam, Velmarini Vasquez, Joy Mitra, Istvan Boldogh, K S Rao, Thomas A Kent, Sankar Mitra, Muralidhar L Hegde
A foremost challenge for the neurons, which are among the most oxygenated cells, is the genome damage caused by chronic exposure to endogenous reactive oxygen species (ROS), formed as cellular respiratory byproducts. Strong metabolic activity associated with high transcriptional levels in these long lived post-mitotic cells render them vulnerable to oxidative genome damage, including DNA strand breaks and mutagenic base lesions. There is growing evidence for the accumulation of unrepaired DNA lesions in the central nervous system (CNS) during accelerated aging and progressive neurodegeneration...
September 20, 2016: Mechanisms of Ageing and Development
Luisa Rubino, Nicoletta Guaragnella, Sergio Giannattasio
A universal feature of the replication of positive-strand RNA viruses is the association with intracellular membranes. Carnation Italian ringspot virus (CIRV) replication in plants occurs in vesicles derived from the mitochondrial outer membrane. The product encoded by CIRV ORF1, p36, is required for targeting the virus replication complex to the outer mitochondrial membrane both in plant and yeast cells. Here the yeast Saccharomyces cerevisiae was used as a model host to study the effect of CIRV p36 on cell survival and death...
September 13, 2016: Mechanisms of Ageing and Development
Aris A Polyzos, Cynthia T McMurray
Mitochondrial dysfunction and ensuing oxidative damage is typically thought to be a primary cause of Huntington's disease, Alzheimer's disease and Parkinson disease. There is little doubt that mitochondria (MT) become defective as neurons die, yet whether MT defects are the primary cause or a detrimental consequence of toxicity remains unanswered. Oxygen consumption rate (OCR) and glycolysis provide sensitive and informative measures of the functional status MT and the cells metabolic regulation, yet these measures differ depending on the sample source; species, tissue type, age at measurement, and whether MT are measured in purified form or in a cell...
September 12, 2016: Mechanisms of Ageing and Development
Stephan Gasser, Wendy Y L Zhang, Nikki Yi Jie Tan, Shubhita Tripathi, Manuel A Suter, Zhi Huan Chew, Muznah Khatoo, Joanne Ngeow, Florence S G Cheung
The presence of damaged and microbial DNA can pose a threat to the survival of organisms. Cells express various sensors that recognize specific aspects of such potentially dangerous DNA. Recognition of damaged or microbial DNA by sensors induces cellular processes that are important for DNA repair and inflammation. Here, we review recent evidence that the cellular response to DNA damage and microbial DNA are tightly intertwined. We also discuss insights into the parameters that enable DNA sensors to distinguish damaged and microbial DNA from DNA present in healthy cells...
September 7, 2016: Mechanisms of Ageing and Development
E Dall'Ara, M Boudiffa, C Taylor, D Schug, E Fiegle, A J Kennerley, C Damianou, G M Tozer, F Kiessling, R Müller
Several non-invasive imaging techniques are used to investigate the effect of pathologies and treatments over time in mouse models. Each preclinical in vivo technique provides longitudinal and quantitative measurements of changes in tissues and organs, which are fundamental for the evaluation of alterations in phenotype due to pathologies, interventions and treatments. However, it is still unclear how these imaging modalities can be used to study ageing with mice models. Almost all age related pathologies in mice such as osteoporosis, arthritis, diabetes, cancer, thrombi, dementia, to name a few, can be imaged in vivo by at least one longitudinal imaging modality...
August 13, 2016: Mechanisms of Ageing and Development
Marjorie Petitjean, Marie-Ange Teste, Isabelle Léger-Silvestre, Jean M François, Jean-Luc Parrou
Looking back to our recent work that challenged the paradigm of trehalose in stress resistance in yeast, our objective was to revisit the role of this disaccharide in chronological life span (CLS), and in the control of apoptosis. Using a catalytically dead variant of the trehalose-6-phosphate synthase (Tps1) protein, (the first enzyme in the trehalose biosynthetic pathway), and by manipulating intracellular trehalose independently of this pathway, we demonstrated that trehalose has no role in CLS or in the inhibition of acetic acid or H202-triggered cell death...
August 6, 2016: Mechanisms of Ageing and Development
Daniel G J Smethurst, Katrina F Cooper
Following extracellular stress signals, all eukaryotic cells choose whether to elicit a pro-survival or pro-death response. The decision over which path to take is governed by the severity and duration of the damage. In response to mild stress, pro-survival programs are initiated (unfolded protein response, autophagy, mitophagy) whereas severe or chronic stress forces the cell to abandon these adaptive programs and shift towards regulated cell death to remove irreversibly damaged cells. Both pro-survival and pro-death programs involve regulated communication between the endoplasmic reticulum (ER) and mitochondria...
August 6, 2016: Mechanisms of Ageing and Development
Sara Verbandt, Sónia Troeira Henriques, Pieter Spincemaille, Peta J Harvey, Gursimran Chandhok, Vanessa Sauer, Barbara De Coninck, David Cassiman, David J Craik, Bruno P A Cammue, Kaat De Cremer, Karin Thevissen
The plant-derived decapeptide OSIP108 increases tolerance of yeast and human cells to apoptosis-inducing agents, such as copper and cisplatin. We performed a whole amino acid scan of OSIP108 and conducted structure-activity relationship studies on the induction of cisplatin tolerance (CT) in yeast. The use of cisplatin as apoptosis-inducing trigger in this study should be considered as a tool to better understand the survival-promoting nature of OSIP108 and not for purposes related to anti-cancer treatment...
August 1, 2016: Mechanisms of Ageing and Development
Fabiola Olivieri, Giulio Pompilio, Carmela Rita Balistreri
No abstract text is available yet for this article.
October 2016: Mechanisms of Ageing and Development
Elena De Falco, Roberto Carnevale, Francesca Pagano, Isotta Chimenti, Luca Fianchini, Antonella Bordin, Camilla Siciliano, Roberto Monticolo, Francesco Equitani, Albino Carrizzo, Mariangela Peruzzi, Carmine Vecchione, Speranza Rubattu, Sebastiano Sciarretta, Giacomo Frati
Senescence exerts a great impact on both biological and functional properties of circulating endothelial progenitor cells (EPCs), especially in cardiovascular diseases where the physiological process of aging is accelerated upon clinical administration of certain drugs such as doxorubicin. EPC impairment contributes to doxorubicin-induced cardiotoxicity. Doxorubicin accelerates EPC aging, although mechanisms underlying this phenomenon remain to be fully clarified. Here we investigated if Nox2 activity is able to modulate the premature senescence induced in vitro by doxorubicin in human EPCs...
October 2016: Mechanisms of Ageing and Development
Carla Regina, Emanuele Panatta, Eleonora Candi, Gerry Melino, Ivano Amelio, Carmela Rita Balistreri, Margherita Annicchiarico-Petruzzelli, Nicola Di Daniele, Giovanni Ruvolo
Ageing leads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence and manifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. This ageing-dependent impairment of endothelial functions is considered a key factor contributing to vascular dysfunctions, which is responsible of several age-related diseases of the vascular system and other organs...
October 2016: Mechanisms of Ageing and Development
Angelo Ferrante, Giuliana Guggino, Diana Di Liberto, Francesco Ciccia, Paola Cipriani, Carmela Rita Balistreri, Guido Sireci, Roberto Giacomelli, Giovanni Triolo
Endothelial Progenitor Cells (EPCs) are bone marrow derived cells able to differentiate in mature endothelial cells (EC) contributing to the generation of new vessels, connecting to fibronectin, and forming colonies and/or colony forming units. Since circulating EPCs can be actively considered part of endothelial damage in several cardiovascular diseases and autoimmune disorders the possibility to have a measure for endothelium damage should be considered of interest to predict the patient out-come. At the same time the EPCs proliferative and regenerative role could be considered for therapeutic applications...
October 2016: Mechanisms of Ageing and Development
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