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Mechanisms of Ageing and Development

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https://www.readbyqxmd.com/read/28803844/the-atf6%C3%AE-arm-of-the-unfolded-protein-response-mediates-replicative-senescence-in-human-fibroblasts-through-a-cox2-prostaglandin-e2-intracrine-pathway
#1
Johanna Cormenier, Nathalie Martin, Julie Deslé, Clara Salazar-Cardozo, Albin Pourtier, Corinne Abbadie, Olivier Pluquet
Senescence is recognized as a cellular state acquired in response to various stresses. It occurs in correlation with the activation of the Unfolded Protein Response (UPR) pathway. However, the UPR targets which might relay the establishment of the senescent phenotype are not known. Herein, we investigated whether the up-regulation of the COX2 (PTGS2) limiting enzyme in the prostaglandin biosynthesis pathway, known to mediate cellular senescence in normal human fibroblasts, could be controlled by the UPR sensors ATF6α, IRE1α and PERK...
August 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28800967/role-of-prion-protein-in-premature-senescence-of-human-fibroblasts
#2
Emmanuelle Boilan, Virginie Winant, Elise Dumortier, Benaissa ElMoualij, Pascale Quatresooz, Heinz D Osiewacz, Florence Debacq-Chainiaux, Olivier Toussaint
Prion protein (PrP) is essentially known for its capacity to induce neurodegenerative prion diseases in mammals caused by a conformational change in its normal cellular isoform (PrP(C)) into an infectious and disease-associated misfolded form, called scrapie isoform (PrP(Sc)). Although its sequence is highly conserved, less information is available on its physiological role under normal conditions. However, increasing evidence supports a role for PrP(C) in the cellular response to oxidative stress. In the present study, a new link between PrP and senescence is highlighted...
August 8, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28789837/investigating-the-amyloid-beta-enhancing-effect-of-cgmp-in-neuro2a-cells
#3
Elisa Calcagno, Francesca Caudano, Mario Passalacqua, Maria A Pronzato, Ernesto Fedele, Roberta Ricciarelli
Long-term potentiation (LTP) and the process of memory formation require activation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Notably, recent evidence indicated that both cyclic nucleotides boost the production of amyloid-beta (Aβ) peptides. In particular, cAMP was shown to favor hippocampal LTP by stimulating the synthesis of the amyloid precursor protein APP, whereas cGMP was found to enhance LTP and to improve memory by increasing Aβ levels without affecting the expression of APP...
August 5, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28780382/dicarbonyls-induce-senescence-of-human-vascular-endothelial-cells
#4
Alexander Navarrete Santos, Kathleen Jacobs, Andreas Simm, Nicole Glaubitz, Rüdiger Horstkorte, Britt Hofmann
RATIONALE: Glyoxal (GO) and Methylglyoxal (MGO) are two dicarbonyls involved in the formation of advanced glycation end products (AGEs). Endothelial cells in the vessels are in constant contact with circulating AGEs and dicarbonyls. With this project, we aimed to elucidate the effect of GO and MGO on primary human vascular endothelial cells (HVECs). METHODS: Graft material from patients with coronary heart disease was used as HVECs source. HVECs were treated with different concentrations of GO and MGO...
August 2, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28765009/involvement-of-trnas-in-replication-of-human-mitochondrial-dna-and-modifying-effects-of-telomerase
#5
Meenakshisundaram Balasubramaniam, Robert J Shmookler Reis, D Phil, Srinivas Ayyadevara, Xianwei Wang, Akshatha Ganne, Magomed Khaidakov
Overexpression of telomerase has been shown to significantly increase the lifespan of mice. When mechanistically attributed to repair of critically short telomeres, the lifespan extending action of telomerase cannot be reconciled with the observation that telomerase-null mice do not exhibit shortening of lifespan for at least two generations. We hypothesized that telomerase may interfere with replication of mitochondrial DNA (mtDNA) in a way that reduces formation of deletions - the primary cause of age-dependent cell attrition in non-renewable cells such as myocytes and neurons...
July 29, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28757326/proteome-oxidative-carbonylation-during-oxidative-stress-induced-premature-senescence-of-wi-38-human-fibroblasts
#6
Marine Le Boulch, Emad K Ahmed, Adelina Rogowska-Wrzesinska, Martín A Baraibar, Bertrand Friguet
Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi-proteome") during ageing and age-related diseases represent a restricted set of cellular proteins, indicating that certain proteins are more prone to oxidative carbonylation and subsequent intracellular accumulation. The occurrence of specific carbonylated proteins upon oxidative stress induced premature senescence of WI-38 human fibroblasts and their follow-up identification have been addressed in this study...
July 27, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28755850/sips-as-a-model-to-study-age-related-changes-in-proteolysis-and-aggregate-formation
#7
REVIEW
Christiane Ott, Tobias Jung, Tilman Grune, Annika Höhn
Aging is accompanied by the accumulation of cellular damage over time in response to stress, lifestyle and environmental factors ultimately leading to age-related diseases and death. Additionally, the number of senescent cells increases with age. Senescence is most likely not a static endpoint, it represents a series of hallmarks including morphological changes, alterations in protein turnover and accumulation of protein aggregates. The importance of protein oxidation and aggregate accumulation in the progression of aging is not yet fully understood and research to what extent the accumulation of oxidized proteins has an effect on senescence and the aging process is still ongoing...
July 26, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28754532/centenarians-maintain-mirna-biogenesis-pathway-while-it-is-impaired-in-octogenarians
#8
C Borrás, E Serna, J Gambini, M Inglés, J Vina
Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging)...
July 25, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28754531/carf-is-a-multi-module-regulator-of-cell-proliferation-and-a-molecular-bridge-between-cellular-senescence-and-carcinogenesis
#9
REVIEW
Renu Wadhwa, Rajkumar Singh Kalra, Sunil C Kaul
CARF (Collaborator of ARF) was first identified as an ARF (Alternative Reading Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening. Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an ARF-dependent or -independent manner. It acts as a transcriptional repressor of HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated degradation. CARF-driven control over p53-HDM2-p21(WAF1) axis was shown to regulate cell proliferative fates. Cells with CARF-overexpression (CARF-OE) and superexpression (CARF-SE) showed growth arrest and pro-proliferative phenotypes, respectively...
July 25, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28739375/oxidative-stress-and-inhibition-of-nitric-oxide-generation-underlie-methotrexate-induced-senescence-in-human-colon-cancer-cells
#10
Magdalena Dabrowska, Lukasz Uram, Zbigniew Zielinski, Wojciech Rode, Ewa Sikora
The response of human colon cancer C85 cells to methotrexate takes the form of reversible growth arrest of the type of stress-induced senescence. In the present study it is shown that during C85 cell progression into methotrexate-induced senescence, dihydrofolate reductase, the primary intracellular target for the drug, is stabilized at the protein level and its enzymatic activity, assayed in crude cellular extracts, decreases by 2-fold. Dihydrofolate reductase inhibition results in an increase in dihydrobiopterin level and an ultimate decrease in the tetrahydrobiopterin: dihydrobiopterin ratio in senescent cells...
July 21, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28705548/age-dependent-ventricular-arrhythmias-risk-structural-and-molecular-remodeling-in-systemic-arterial-hypertension
#11
Alina Scridon, Rosa Doñate Puertas, Waheed Manati, Emmanuelle Fouilloux-Meugnier, Emmanuelle Loizon, Valérie Oréa, Bruno Chapuis, Claude Julien, Christian Barrès, Alain Tabib, Philippe Chevalier
INTRODUCTION: The left ventricular hypertrophy (LVH)-ventricular arrhythmias relationship associated with arterial hypertension and aging remains controversial. We aimed to assess the age-dependency of ventricular arrhythmias in spontaneously hypertensive rats (SHRs) and the corresponding ventricular structural and molecular remodeling. MATERIALS AND METHODS: Ventricular arrhythmias were quantified using 24-h radiotelemetry ECG monitoring in eight SHRs and four Wistar-Kyoto (WKY) rats at 14 (young), 24 (adult), and 48 (aging) weeks of age...
July 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28688962/stress-cell-senescence-and-organismal-ageing
#12
REVIEW
João Pedro de Magalhães, João F Passos
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing...
July 5, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28684270/in-memoriam-olivier-toussaint-stress-induced-premature-senescence-and-the-role-of-dna-damage
#13
Alexander Bürkle
In the present paper, a concise review on the major contribution of our recently deceased colleague, Dr Olivier Toussaint, to the topic of stress-induced premature senescence (SIPS) of cells is presented together with a hypothesis on a mechanistic role of DNA damage, based on accumulating evidence for an important role of DNA damage as a driving factor in ageing.
July 3, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28684269/a-novel-role-of-the-mitochondrial-permeability-transition-pore-in-gossypol-induced-mitochondrial-dysfunction
#14
Verena Warnsmann, Nina Meyer, Andrea Hamann, Donat Kögel, Heinz D Osiewacz
Gossypol, a natural polyphenolic compound from cotton seeds, is known to trigger different forms of cell death in various types of cancer. Gossypol acts as a Bcl-2 inhibitor that induces apoptosis in apoptosis-competent cells. In apoptosis-resistant cancers such as glioblastoma, it triggers a non-apoptotic type of cell death associated with increased oxidative stress, mitochondrial depolarisation and fragmentation. In order to investigate the impact of gossypol on mitochondrial function, the mitochondrial permeability transition pore and on oxidative stress in more detail, we used the aging model Podospora anserina that lacks endogenous Bcl-2 proteins...
July 3, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28651996/centenarians-as-a-21st-century-healthy-aging-model-a-legacy-of-humanity-and-the-need-for-a-world-wide-consortium-wwcc100
#15
EDITORIAL
Claudio Franceschi, Giuseppe Passarino, Daniela Mari, Daniela Monti
No abstract text is available yet for this article.
June 23, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28636901/the-effect-of-cd34-cell-telomere-length-and-htert-expression-on-the-outcome-of-autologous-cd34-cell-transplantation-in-patients-with-chronic-heart-failure
#16
Jasmina-Ziva Rozman, Maja Pohar Perme, Mojca Jez, Elvira Malicev, Metka Krasna, Srdjan Novakovic, Bojan Vrtovec, Primoz Rozman
Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34(+) cell telomere length and hTERT expression on the clinical outcome of autologous CD34(+) cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34(+) cells were mobilized with granulocyte colony-stimulating factor, enriched by immunoselection and delivered transendocardially...
June 18, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28445698/editorial-dna-damage-immunity
#17
EDITORIAL
George A Garinis, Bjoern Schwer, Björn Schumacher
No abstract text is available yet for this article.
July 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27863852/the-rag-recombinase-beyond-breaking
#18
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)...
July 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27720808/immune-and-inflammatory-responses-to-dna-damage-in-cancer-and-aging
#19
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...
July 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27702596/dna-damage-induced-inflammation-and-nuclear-architecture
#20
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...
July 2017: Mechanisms of Ageing and Development
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