Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells
In conclusion, our studies demonstrated that tolerance/survival-promoting properties of OSIP108 can be significantly improved by single amino acid substitutions, and that these properties are dependent on (an) intracellular target(s), yet to be determined. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

ER fatalities —The role of ER-mitochondrial contact sites in yeast life and death decisions
Publication date: Available online 6 August 2016 Source:Mechanisms of Ageing and Development Author(s): 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...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

A new function for the yeast trehalose-6P synthase (Tps1) protein, as key pro-survival factor during growth, chronological ageing, and apoptotic stress
Publication date: Available online 6 August 2016 Source:Mechanisms of Ageing and Development Author(s): 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 t...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Longitudinal imaging of the ageing mouse
Publication date: Available online 13 August 2016 Source:Mechanisms of Ageing and Development Author(s): 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 sti...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Effect of age and latent CMV infection on CD8+  CD56+ T cells (NKT-like) frequency and functionality
Publication date: September 2016 Source:Mechanisms of Ageing and Development, Volume 158 Author(s): Fakhri Hassouneh, Carmen Campos, Nelson López-Sejas, Corona Alonso, Raquel Tarazona, Rafael Solana, Alejandra Pera Changes in the T cell pool caused by CMV infection have been proposed to contribute to immunosenescence, but it has been postulated that CMV can also have some beneficial effects in young individuals improving the immune response to other pathogens. T cells expressing CD56 (NKT-like cells) are cytotoxic effector cells with a significant role in the immune response against cancer. We have studied how age ...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Development of the adaptive NK cell response to human cytomegalovirus in the context of aging
Publication date: September 2016 Source:Mechanisms of Ageing and Development, Volume 158 Author(s): Miguel López-Botet, Aura Muntasell, José E. Martínez-Rodríguez, María López-Montañés, Marcel Costa-García, Aldi Pupuleku Human cytomegalovirus (HCMV) establishes a highly prevalent life-long latent infection. Though generally subclinical, HCMV infection may have severe consequences during fetal development and in immunocompromised individuals. Based on epidemiological studies HCMV(+) serology has been associated with the development of atherosclerosis, immune se...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Cytomegalovirus driven immunosenescence —An immune phenotype with or without clinical impact?
Publication date: September 2016 Source:Mechanisms of Ageing and Development, Volume 158 Author(s): Cecilia Söderberg-Nauclér, Olesja Fornara, Afsar Rahbar The continuous emerging increase in life span has led to vulnerability to a number of different diseases in the elderly. Some of these risks may be attributed to specific changes in the immune system referred to as immunoscenescence. This term aims to describe decreased immune functions among elderly individuals, and is characterized to be harmful age-associated changes in the immune system that lead to its gradual immune dysfunction. An impaired function o...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Sensing of Dangerous DNA
Publication date: Available online 7 September 2016 Source:Mechanisms of Ageing and Development Author(s): 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 re...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

The chicken or the egg: mitochondrial dysfunction and oxidative damage as a cause or consequence of on toxicity in Huntington ’s disease.
Publication date: Available online 12 September 2016 Source:Mechanisms of Ageing and Development Author(s): 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 th...
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Endothelial progenitor cells in ageing
Publication date: Available online 12 September 2016 Source:Mechanisms of Ageing and Development Author(s): Fabiola Olivieri, Giulio Pompilio, Carmela Rita Balistreri (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - September 13, 2016 Category: Geriatrics Source Type: research

Methylation analysis of DNA repair genes in Alzheimer ’s disease
Publication date: Available online 11 April 2016 Source:Mechanisms of Ageing and Development Author(s): Fabio Coppedè, Pierpaola Tannorella, Andrea Stoccoro, Lucia Chico, Gabriele Siciliano, Ubaldo Bonuccelli, Lucia Migliore There is substantial evidence of impaired DNA repair activities in Alzheimer’s disease (AD) neurons and peripheral tissues, inducing some investigators to speculate that this could partially result from promoter hypermethylation of DNA repair genes, resulting in gene silencing in those tissues. In the present study a screening cohort composed by late-onset AD (LOAD) patients and h...
Source: Mechanisms of Ageing and Development - June 18, 2016 Category: Geriatrics Source Type: research

Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration
Publication date: Available online 18 June 2016 Source:Mechanisms of Ageing and Development Author(s): Richard A. Perry, Lemuel A. Brown, David E. Lee, Jacob L. Brown, Jamie I. Baum, Nicholas P. Greene, Tyrone A. Washington Aging decreases the ability of skeletal muscle to respond to injury. Leucine has been demonstrated to target protein synthetic pathways in skeletal muscle thereby enhancing this response. However, the effect of aging on leucine-induced alterations in protein synthesis at the onset of skeletal muscle regeneration has not been fully elucidated. The purpose of this study was to determine if aging ...
Source: Mechanisms of Ageing and Development - June 18, 2016 Category: Geriatrics Source Type: research

Nicotinamide supplementation phenocopies SIR2 inactivation by modulating carbon metabolism and respiration during yeast chronological aging
Publication date: Available online 16 June 2016 Source:Mechanisms of Ageing and Development Author(s): Ivan Orlandi, Damiano Pellegrino Coppola, Maurizio Strippoli, Rossella Ronzulli, Marina Vai Nicotinamide (NAM), a form of vitamin B3, is a byproduct and noncompetitive inhibitor of the deacetylation reaction catalyzed by Sirtuins. These represent a family of evolutionarily conserved NAD+-dependent deacetylases that are well-known critical regulators of metabolism and aging and whose founding member is Sir2 of Saccharomyces cerevisiae. Here, we investigated the effects of NAM supplementation in the context of yeast ...
Source: Mechanisms of Ageing and Development - June 17, 2016 Category: Geriatrics Source Type: research

Cytomegalovirus driven immunosenescence: An immune phenotype with or without clinical impact?
Publication date: Available online 16 June 2016 Source:Mechanisms of Ageing and Development Author(s): Cecilia Söderberg-Nauclér, Olesja Fornara, Afsar Rahbar The continuous emerging increase in life span have led to vulnerability to a number of different diseases in the elderly. Some of these risks may be attributed to specific changes in the immune system referred to as immunoscenescence. This term aims to describe decreased immune functions among elderly individuals, and is characterized to be harmful age-associated changes in the immune system that lead to its gradual immune dysfunction. An impaired fu...
Source: Mechanisms of Ageing and Development - June 16, 2016 Category: Geriatrics Source Type: research

DNA damage in protective and adverse inflammatory responses: Friend of foe?
Publication date: Available online 15 June 2016 Source:Mechanisms of Ageing and Development Author(s): Tetiana Poliezhaieva, Maria Ermolaeva The impact of DNA damage-induced immune responses on aging and disease development is a topic of top scientific interest and debate. While abundant data links persistent genotoxic stress and associated inflammatory activity to organ decline and cancer development, evidence of pro-homeostatic effects of immune responses triggered by transient DNA damage gradually accumulates. Current review focuses on comparing systemic consequences of transient genotoxicity with effects of persist...
Source: Mechanisms of Ageing and Development - June 15, 2016 Category: Geriatrics Source Type: research

Yeast as a model for the identification of novel survival-promoting compounds applicable to treat degenerative diseases
Publication date: Available online 7 June 2016 Source:Mechanisms of Ageing and Development Author(s): Sara Verbandt, Bruno P.A. Cammue, Karin Thevissen Programmed cell death (PCD) plays an important role in development and normal metabolic functioning of organisms. Excessive cell death is the cause of many degenerative diseases, like neurodegenerative disorders and Wilson’s disease, for which current therapies remain insufficient. Current therapies are mainly focused on decreasing the disease symptoms following cell death, rather than blocking the cell death process itself. The latter can be obtained by either d...
Source: Mechanisms of Ageing and Development - June 8, 2016 Category: Geriatrics Source Type: research

Chemical screening identifies the β-Carboline Alkaloid Harmine to be synergistically lethal with Doxorubicin
Publication date: Available online 6 June 2016 Source:Mechanisms of Ageing and Development Author(s): Reham Atteya, Mohamed E. Ashour, Elsayed E. Ibrahim, Mohamed A. Farag, Sherif F. El-Khamisy Despite being an invaluable chemotherapeutic agent for several types of cancer, the clinical utility of doxorubicin is hampered by its age-related and dose-dependent cardiotoxicity. Co-administration of dexrazoxane as a cardioprotective agent has been proposed, however recent studies suggest that it attenuates doxorubicin-induced antitumor activity. Since compounds of natural origin present a rich territory for drug discovery...
Source: Mechanisms of Ageing and Development - June 6, 2016 Category: Geriatrics Source Type: research

Double Strand Breaks May Be a Missing Link between Entropy and Aging
Publication date: Available online 4 June 2016 Source:Mechanisms of Ageing and Development Author(s): Peter Lenart, Julie Bienertová-Vašků It has been previously suggested that an increase in entropy production leads to aging. However, the mechanisms linking increased entropy production in living mass to aging are currently unclear. Even though entropy cannot be easily associated with any specific molecular damage, the increase of entropy in structural mass may be connected with heat stress, which is known to generate double strand breaks. Double strand breaks, which are in turn known to play an importan...
Source: Mechanisms of Ageing and Development - June 5, 2016 Category: Geriatrics Source Type: research

Does Cytomegalovirus Infection Contribute to Socioeconomic Disparities in All-cause Mortality?
Publication date: Available online 4 June 2016 Source:Mechanisms of Ageing and Development Author(s): Lydia Feinstein, Christian E Douglas, Rebecca C Stebbins, Graham Pawele, Amanda M. Simanek, Allison E Aiello The social patterning of cytomegalovirus (CMV) and its implication in aging suggest that the virus may partially contribute to socioeconomic disparities in mortality. We used Cox regression and inverse odds ratio weighting to quantify the proportion of the association between socioeconomic status (SES) and all-cause mortality that was attributable to mediation by CMV seropositivity. Data were from the Nation...
Source: Mechanisms of Ageing and Development - June 5, 2016 Category: Geriatrics Source Type: research

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?
Publication date: Available online 3 May 2016 Source:Mechanisms of Ageing and Development Author(s): 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...
Source: Mechanisms of Ageing and Development - May 27, 2016 Category: Geriatrics Source Type: research

DNA damage in the oligodendrocyte lineage and its role in brain aging
Publication date: Available online 26 May 2016 Source:Mechanisms of Ageing and Development Author(s): Kai-Hei Tse, Karl Herrup Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network. Even slight defects in myelin integrity impair performance and enhance the risk of neurological disorders. Indeed, myelin degeneration is an early and well-recognized neuropathology that is age associated, but appears before cognitive decline. Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the alte...
Source: Mechanisms of Ageing and Development - May 26, 2016 Category: Geriatrics Source Type: research

Role of NOX2 in mediating doxorubicin-induced senescence in human endothelial progenitor cells
In conclusion, Nox2 activity efficiently contributes to the mechanism of oxidative stress-induced increase in premature aging conferred by doxorubicin. The importance of modulation of Nox2 in human EPCs could reveal a useful tool to restore EPC physiological function and properties. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - May 24, 2016 Category: Geriatrics Source Type: research

Molecular pathophysiology of impaired glucose metabolism, mitochondrial dysfunction, and oxidative DNA damage in Alzheimer's disease brain
Publication date: Available online 24 May 2016 Source:Mechanisms of Ageing and Development Author(s): Nona Abolhassani, Julio Leon, Zijing Sheng, Sugako Oka, Hideomi Hamasaki, Toru Iwaki, Yusaku Nakabeppu In normal brain, neurons in the cortex and hippocampus produce insulin, which modulates glucose metabolism and cognitive functions. It has been shown that insulin resistance impairs glucose metabolism and mitochondrial function, thus increasing production of reactive oxygen species. Recent progress in Alzheimer’s disease (AD) research revealed that insulin production and signaling are severely impaired in A...
Source: Mechanisms of Ageing and Development - May 24, 2016 Category: Geriatrics Source Type: research

Yeast buddies helping to unravel the complexity of neurodegenerative disorders
Publication date: Available online 12 May 2016 Source:Mechanisms of Ageing and Development Author(s): Gernot Fruhmann, David Seynnaeve, Ju Zheng, Karen Ven, Sofie Molenberghs, Tobias Wilms, Beidong Liu, Joris Winderickx, Vanessa Franssens Neurodegenerative disorders have a profound effect on the quality of life of patients and their environment. However, the development of adequate therapies requires accurate understanding of the underlying disease pathogenesis. On that account, yeast models can play an important role, as they enable the elucidation of the mechanisms leading to neurodegenerative disorders. Furth...
Source: Mechanisms of Ageing and Development - May 12, 2016 Category: Geriatrics Source Type: research

“role of nox2 in mediating doxorubicin-induced senescence in human endothelial progenitor cells”
In conclusion, Nox2 activity efficiently contributes to the mechanism of oxidative stress-induced increase in premature aging conferred by doxorubicin. The importance of modulation of Nox2 in human EPCs could reveal a useful tool to restore EPC physiological function and properties. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - May 12, 2016 Category: Geriatrics Source Type: research

Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases
Publication date: Available online 4 May 2016 Source:Mechanisms of Ageing and Development Author(s): Carla Regina, Emanuele Panatta, Eleonora Candi, Gerry Melino, Ivano Amelio, Carmela Rita Balistreri, Margherita Annicchiarico-Petruzzelli, Nicola Di Daniele, Giovanni Ruvolo Ageingleads to a progressive deterioration of structure and function of all organs over the time. During this process endothelial cells undergo senescence andmanifest significant changes in their properties, resulting in impairment of the vascular functionality and neo-angiogenic capability. Thisageing-dependent impairment of endothelial func...
Source: Mechanisms of Ageing and Development - May 5, 2016 Category: Geriatrics Source Type: research

Characterization of age-dependent changes in the striatum: Response to the mitochondrial toxin 3-nitropropionic acid
Publication date: Available online 30 April 2016 Source:Mechanisms of Ageing and Development Author(s): G.K. Shinomol, S. Ranganayaki, Apurva K. Joshi, N. Gayathri, Harsha Gowda, Muralidhara, Srinivas Bharath M.M. Neurodegenerative phenomena are associated with mitochondrial dysfunction and this could be exacerbated by aging. Age-dependence of mitochondrial response to toxins could help understand these mechanisms and evolve novel therapeutics. 3-nitropropionic acid (3-NPA) is a mitochondrial toxin that induces neurotoxicity in the striatum via inhibition of complex II. We investigated the age-related events that ...
Source: Mechanisms of Ageing and Development - May 1, 2016 Category: Geriatrics Source Type: research

Dynamics of Biomarkers in Relation to Aging and Mortality
Publication date: Available online 29 April 2016 Source:Mechanisms of Ageing and Development Author(s): Konstantin G. Arbeev, Svetlana V. Ukraintseva, Anatoliy I. Yashin Contemporary longitudinal studies collect repeated measurements of biomarkers allowing one to analyze their dynamics in relation to mortality, morbidity, or other health-related outcomes. Rich and diverse data collected in such studies provide opportunities to investigate how various socio-economic, demographic, behavioral and other variables can interact with biological and genetic factors to produce differential rates of aging in individuals. In thi...
Source: Mechanisms of Ageing and Development - April 30, 2016 Category: Geriatrics Source Type: research

Structural Equation Modeling Identifies Markers of Damage and Function in the Aging Male Fischer 344 Rat
Publication date: Available online 28 April 2016 Source:Mechanisms of Ageing and Development Author(s): Elizabeth A. Grunz-Borgmann, LaNita A. Nichols, Charles E. Wiedmeyer, Sean Spagnoli, Jerome P. Trzeciakowski, Alan R. Parrish The male Fischer 344 rat is an established model to study progressive renal dysfunction that is similar, but not identical, to chronic kidney disease (CKD) in humans. These studies were designed to assess age-dependent alterations in renal structure and function at late-life timepoints, 16-24 months. Elevations in BUN and plasma creatinine were not significant until 24 months, however, ele...
Source: Mechanisms of Ageing and Development - April 29, 2016 Category: Geriatrics Source Type: research

Polynucleotide Kinase-Phosphatase (PNKP) Mutations and Neurologic Disease
Publication date: Available online 26 April 2016 Source:Mechanisms of Ageing and Development Author(s): Lavinia C. Dumitrache, Peter J. McKinnon A variety of human neurologic diseases are caused by inherited defects in DNA repair. In many cases, these syndromes almost exclusively impact the nervous system, underscoring the critical requirement for genome stability in this tissue. A striking example of this is defective enzymatic activity of polynucleotide kinase-phosphatase (PNKP), leading to microcephaly or neurodegeneration. Notably, the broad neural impact of mutations in PNKP can result in markedly different diseas...
Source: Mechanisms of Ageing and Development - April 27, 2016 Category: Geriatrics Source Type: research

A brewing understanding of the regulation of Bax function by Bcl-xL and Bcl-2
Publication date: Available online 23 April 2016 Source:Mechanisms of Ageing and Development Author(s): Thibaud T. Renault, Laurent M. Dejean, Stéphen Manon Bcl-2 family members form a network of protein-protein interactions that regulate apoptosis through permeabilization of the mitochondrial outer membrane. Deciphering this intricate network requires streamlined experimental models, including the heterologous expression in yeast. This approach had previously enabled researchers to identify domains and residues that underlie the conformational changes driving the translocation, the insertion and the oligomeriz...
Source: Mechanisms of Ageing and Development - April 24, 2016 Category: Geriatrics Source Type: research

Caloric restriction alleviates alpha-synuclein toxicity in aged yeast cells by controlling the opposite roles of Tor1 and Sir2 on autophagy
Publication date: Available online 21 April 2016 Source:Mechanisms of Ageing and Development Author(s): Ana Guedes, Paula Ludovico, Belém Sampaio-Marques Alpha-synuclein (syn) is the main component of proteinaceous inclusions known as Lewy bodies (LBs), which are implicated in the pathogenesis of the neurodegenerative diseases known as synucleinopathies, like Parkinson’s disease (PD). Aging is a major risk factor for PD and thus, interventions that delay aging will have promising effects in PD and other synucleinopathies. Caloric restriction (CR) is the only non-genetic intervention shown to promote lifes...
Source: Mechanisms of Ageing and Development - April 22, 2016 Category: Geriatrics Source Type: research

Genetic instability and aging under the scrutiny of comparative biology: a meta-analysis of spontaneous micronuclei frequency
Publication date: Available online 22 April 2016 Source:Mechanisms of Ageing and Development Author(s): Eleonora Croco, Silvia Marchionni, Antonello Lorenzini In gerontology, comparative biology of longevity offers a powerful observation point thus far underexploited. We use this approach to evaluate the role of genetic stability in longevity determination, extrapolating existing data from the literature. Screening eight pre-existing studies, we collected data from 47 mammalian species and analyzed the relationship of spontaneous micronucleated erythrocyte frequency to species maximum longevity and species adult body ...
Source: Mechanisms of Ageing and Development - April 22, 2016 Category: Geriatrics Source Type: research

Genome instability in Alzheimer disease
Publication date: Available online 20 April 2016 Source:Mechanisms of Ageing and Development Author(s): Yujun Hou, Hyundong Song, Deborah L. Croteau, Mansour Akbari, Vilhelm A. Bohr Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Autosomal dominant, familial AD (fAD) is very rare and caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN-1), and presenilin-2 (PSEN-2) genes. The pathogenesis of sporadic AD (sAD) is more complex and variants of several genes are associated with an increased lifetime risk of AD. Nuclear and mitochondri...
Source: Mechanisms of Ageing and Development - April 21, 2016 Category: Geriatrics Source Type: research

Methylation analysis of DNA repair genes in Alzheimer’s disease
Publication date: Available online 11 April 2016 Source:Mechanisms of Ageing and Development Author(s): Fabio Coppedè, Pierpaola Tannorella, Andrea Stoccoro, Lucia Chico, Gabriele Siciliano, Ubaldo Bonuccelli, Lucia Migliorea There is substantial evidence of impaired DNA repair activities in Alzheimer’s disease (AD) neurons and peripheral tissues, inducing some investigators to speculate that this could partially result from promoter hypermethylation of DNA repair genes, resulting in gene silencing in those tissues. In the present study a screening cohort composed by late-onset AD (LOAD) patients and ...
Source: Mechanisms of Ageing and Development - April 12, 2016 Category: Geriatrics Source Type: research

Apoptosis or Senescence? Which exit route do epithelial cells and fibroblasts preferentially follow?
Publication date: Available online 6 April 2016 Source:Mechanisms of Ageing and Development Author(s): Eleni Georgakopoulou, Konstantinos Evangelou, Sofia Havaki, Paul Townsend, Panagiotis Kanavaros, Vassilis G. Gorgoulis Senescence and apoptosis constitute types of cellular responses that normally ensure homeostasis, when endogenous or exogenous signals occur. Their deregulation is often observed in various pathologies, such as age and non-age related diseases including cancer. Although epithelial cells and fibroblasts are capable to exert both functions, under a plethora of insults, the fact that they exhibit not...
Source: Mechanisms of Ageing and Development - April 7, 2016 Category: Geriatrics Source Type: research

The Effect of Sex on Immune Cells in Healthy Aging: Elderly Women Have More Robust Natural Killer Lymphocytes than Do Elderly Men
Publication date: Available online 6 April 2016 Source:Mechanisms of Ageing and Development Author(s): Ahmad Al-Attar, Steven R. Presnell, Charlotte A. Peterson, D.Travis Thomas, Charles T. Lutz Immune gender differences have been reported, but are little studied in elderly humans. We compared monocyte and lymphocyte subsets, along with soluble immune mediators in healthy men and women over the age of 70. We also measured natural killer (NK) lymphocyte cytotoxic granule exocytosis, chemokine synthesis, and cytokine synthesis in response to a variety of stimuli. Elderly women had significantly more circulating B cell...
Source: Mechanisms of Ageing and Development - April 6, 2016 Category: Geriatrics Source Type: research

BM ageing: implication for cell therapy with EPCs
Publication date: Available online 1 April 2016 Source:Mechanisms of Ageing and Development Author(s): Erica Rurali, Beatrice Bassetti, Gianluca Lorenzo Perrucci, Marco Zanobini, Cristina Malafronte, Felice Achilli, Elisa Gambini The bone marrow (BM) is a well-recognized source of stem/progenitor cells for cell therapy in cardiovascular diseases (CVDs). Preclinical and clinical studies suggest that endothelial progenitor cells (EPCs) contribute to reparative process of vascular endothelium and participate in angiogenesis. As for all organs and cells across the lifespan, BM and EPCs are negatively impacted by agein...
Source: Mechanisms of Ageing and Development - April 2, 2016 Category: Geriatrics Source Type: research

Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway
In conclusion, central injection of M617 mitigated insulin resistance of skeletal muscle by enhancing GLUT4 translocation from intracellular pools to plasma membranes via the activation of the Akt/AS160/GLUT4 signaling pathway. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - April 2, 2016 Category: Geriatrics Source Type: research

Genome Instability: Linking Ageing and Brain Degeneration
Publication date: Available online 31 March 2016 Source:Mechanisms of Ageing and Development Author(s): Ari Barzilai, Björn Schumacher, Yosef Shiloh Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-as...
Source: Mechanisms of Ageing and Development - April 1, 2016 Category: Geriatrics Source Type: research

A multifaceted role for MOF histone modifying factor in genome maintenance
Publication date: Available online 30 March 2016 Source:Mechanisms of Ageing and Development Author(s): Kalpana Mujoo, Clayton R. Hunt, Nobuo Horikoshi, Tej K. Pandita MOF (males absent on the first) was initially identified as a dosage compensation factor in Drosophila that acetylates lysine 16 of histone H4 (H4K16ac) and increased gene transcription from the single copy male X-chromosome. In humans, however, the ortholog of Drosophila MOF has been shown to interact with a range of proteins that extend its potential significance well beyond transcription. For example, recent results indicate MOF is an upstream regul...
Source: Mechanisms of Ageing and Development - March 31, 2016 Category: Geriatrics Source Type: research

Microfluidic Technologies for Yeast Replicative Lifespan Studies
Publication date: Available online 23 March 2016 Source:Mechanisms of Ageing and Development Author(s): Kenneth L Chen, Matthew M Crane, Matt Kaeberlein The budding yeast Saccharomyces cerevisiae has been used as a model organism for the study of aging for over 50 years. In this time, the canonical aging experiment—replicative lifespan analysis by manual microdissection—has remained essentially unchanged. Recently, microfluidic technologies have been developed that may be able to substitute for this time- and labor-intensive procedure. These technologies also allow cell physiology to be observed throughout...
Source: Mechanisms of Ageing and Development - March 24, 2016 Category: Geriatrics Source Type: research

Physical activity and progenitor cell-mediated endothelial repair in chronic heart failure: is there a role for epigenetics?
Publication date: Available online 22 March 2016 Source:Mechanisms of Ageing and Development Author(s): Rina Recchioni, Fiorella Marcheselli, Roberto Antonicelli, Raffaella Lazzarini, Emanuela Mensà, Roberto Testa, Antonio Domenico Procopio, Fabiola Olivieri Chronic heart failure (CHF) is the most common cardiac disease among the elderly and a leading cause of mortality in elderly patients. Endothelial dysfunction is held to have a major role in the development and progression of CHF, which results in progressively impaired functional capacity. Endothelial progenitor cells (EPCs) and circulating angiogenic...
Source: Mechanisms of Ageing and Development - March 23, 2016 Category: Geriatrics Source Type: research

A new perspective of the structural complexity of HCMV-specific T-cell responses
Conclusions Predicting protective immunity based on isolated HCMV subunit-specific T-cell responses is questionable in light of the complex architecture of the overall response. Our findings have important implications for T-cell monitoring, intervention strategies, as well as the application of animal models to the understanding of human infection. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - March 22, 2016 Category: Geriatrics Source Type: research

Mechanisms and Consequences of Aneuploidy and Chromosome Instability in the Aging Brain
We describe the mechanisms accountable for an abnormal DNA content with a particular emphasis on the CNS where cell division is limited. Next, we briefly summarize the types of GIN known to date and discuss how they interconnect with CIN. Lastly we highlight how several forms of CIN may contribute to genetic variation, tissue degeneration and disease in the CNS. (Source: Mechanisms of Ageing and Development)
Source: Mechanisms of Ageing and Development - March 22, 2016 Category: Geriatrics Source Type: research

The impact of intrinsic ageing on the protein composition of the dermal-epidermal junction
Publication date: Available online 21 March 2016 Source:Mechanisms of Ageing and Development Author(s): Abigail K Langton, Poonam Halai, Christopher EM Griffiths, Michael J Sherratt, Rachel EB Watson The dermal-epidermal junction of human skin exhibits age-related remodelling, resulting in a flattened appearance and reduced surface area. Despite this, a paucity of information is available regarding which protein components change with advancing age. Here we report a significant reduction in the protein distribution of collagen IV (P<0.0001), collagen VII (P<0.001), collagen XVII (P<0.01), integr...
Source: Mechanisms of Ageing and Development - March 22, 2016 Category: Geriatrics Source Type: research

Cellular and molecular basis of the imbalance between vascular damage and repair in ageing and age-related diseases: As biomarkers and targets for new treatments
Publication date: Available online 15 March 2016 Source:Mechanisms of Ageing and Development Author(s): Rosalinda Madonna, Giuseppina Novo, Carmela Rita Balistreri Preclinical and clinical studies suggest that specific subsets of cells isolated from the peripheral blood, play an essential role in the imbalance of damage and repair during age-associated diseases, such as metabolic syndrome, diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis and cancer. Endogenous regeneration of the vessel wall involves cells of the vascular wall, inflammatory cells, circulating precursors, and mature endothelial cells...
Source: Mechanisms of Ageing and Development - March 20, 2016 Category: Geriatrics Source Type: research

Structural studies on the mechanism of protein aggregation in age related neurodegenerative diseases
Publication date: Available online 19 March 2016 Source:Mechanisms of Ageing and Development Author(s): Bahareh Eftekharzadeh, Bradley T. Hyman, Susanne Wegmann The progression of many neurodegenerative diseases is assumed to be caused by misfolding of specific characteristic diseases related proteins, resulting in aggregation and fibril formation of these proteins. Protein misfolding associated age related diseases, although different in disease manifestations, share striking similarities. In all cases, one disease protein aggregates and loses its function or additionally shows a toxic gain of function. However, the ...
Source: Mechanisms of Ageing and Development - March 20, 2016 Category: Geriatrics Source Type: research

Cellular and molecular basis of the imbalance between vascular damage and repair in aging and age-related diseases: As biomarkers and targets for new treatments
Publication date: Available online 15 March 2016 Source:Mechanisms of Ageing and Development Author(s): Rosalinda Madonna, Giuseppina Novo, Carmela Rita Balistreri Preclinical and clinical studies suggest, that specific subsets of cells isolated from the peripheral blood play an essential role inthe imbalance of damage and repair during age-associated diseases, such as metabolic syndrome, diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis and cancer. Endogenous regeneration of the vessel wall involves cells of the vascular wall, inflammatory cells, circulating precursors, and mature endothelial cells,...
Source: Mechanisms of Ageing and Development - March 17, 2016 Category: Geriatrics Source Type: research

Novel insights in the dysfunction of human blood-brain barrier after glycation
Publication date: Available online 11 March 2016 Source:Mechanisms of Ageing and Development Author(s): Maryam Hussain, Kaya Bork, Vinayaga S. Gnanapragassam, Dorit Bennmann, Kathleen Jacobs, Alexander Navarette-Santos, Britt Hofmann, Andreas Simm, Kerstin Danker, Rüdiger Horstkorte The blood-brain barrier (BBB) provides a dynamic and complex interface consisting of endothelial cells, pericytes and astrocytes, which are embedded in a collagen and fibronectin-rich basement membrane. This complex structure restricts the diffusion of small hydrophilic solutes and macromolecules as well as the transmigration o...
Source: Mechanisms of Ageing and Development - March 12, 2016 Category: Geriatrics Source Type: research