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Mechanisms of Ageing and Development

Kelly Khomtchouk, Sarah Alter, Michelle Ratliff, Bonnie B Blomberg, Richard L Riley
In young adult BALB/c mice, antibodies to phosphorylcholine (PC) bearing the T15 (TEPC 15) idiotype confer protection against pneumococcal infections. In old age, even though PC reactive B cells are often increased, the proportion of T15(+) antibodies declines. We hypothesize that limited surrogate light chain (SLC) and compromise of the pre-B cell receptor checkpoint in old mice contribute to both reduced new B cell generation and changes in the anti-PC antibodies seen in old age. In old mice: 1) early pre-B cell loss is most pronounced at the preBCR checkpoint; however, the reduced pool of early pre-B cells continues to proliferate consistent with preBCR signaling; 2) increased PC reactivity is seen in bone marrow immature B cells; 3) deficient SLC promotes increased B cell PC reactivity and diminished T15 idiotype within a subset of young adult mice; and 4) in old mice, as pre-B cell losses and reduced SLC become progressively more severe, increased T15 negative PC reactive B cells occur...
November 19, 2016: Mechanisms of Ageing and Development
Runmin Guo, Zijun Wu, Jiamei Jiang, Chang Liu, Bin Wu, Xingyue Li, Teng Li, Hailiang Mo, Songjian He, Shanghai Li, Hai Yan, Ruina Huang, Qiong You, Keng Wu
OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). METHODS: Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay...
November 18, 2016: Mechanisms of Ageing and Development
Chloé Lescale, Ludovic Deriano
DNA double-strand breaks (DSBs) are commonly seen as lesions that threaten genome integrity and contribute to cancer and aging processes. However, in the context of antigen receptor gene assembly, known as V(D)J recombination, DSBs are obligatory intermediates that allow the establishment of genetic diversity and adaptive immunity. V(D)J recombination is initiated when the lymphoid-restricted recombination-activating genes RAG1 and RAG2 are expressed and form a site-specific endonuclease (the RAG nuclease or RAG recombinase)...
November 15, 2016: Mechanisms of Ageing and Development
Oriol Busquets, Miren Ettcheto, Mercè Pallàs, Carlos Beas-Zarate, Ester Verdaguer, Carme Auladell, Jaume Folch, Antoni Camins
AIMS: The sporadic and late-onset form of Alzheimer's disease (AD) constitutes the most common form of dementia. This non-familiar form could be a consequence of metabolic syndrome, characterized by obesity and the development of a brain-specific insulin resistance known as type III diabetes. This work demonstrates the development of a significant AD-like neuropathology due to these metabolic alterations. METHODS: C57BL/6J mice strain were divided into two groups, one fed with a diet rich in palmitic acid (high-fat diet, HFD) since their weaning until 16 months of age, and another group used as a control with a regular diet...
November 15, 2016: Mechanisms of Ageing and Development
Bradley J Willcox, Donald Craig Willcox, Makoto Suzuki
A study of elderly Okinawans has been carried out by the Okinawa Centenarian Study (OCS) research group for over four decades. The OCS began in 1975 as a population-based study of centenarians (99-year-olds and older) and other selected elderly persons residing in the main island of the Japanese prefecture of Okinawa. As of 2015, over 1000 centenarians have been examined. By several measures of health and longevity the Okinawans can claim to be the world's healthiest and longest-lived people. In this paper we explore the demographic, phenotypic, and genetic characteristics of this fascinating population...
November 12, 2016: 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
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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