Mechanisms of ageing and development

Publisher: Elsevier

Current impact factor: 3.40

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.397
2013 Impact Factor 3.51
2012 Impact Factor 3.264
2011 Impact Factor 3.439
2010 Impact Factor 4.857
2009 Impact Factor 4.179
2008 Impact Factor 3.915
2007 Impact Factor 4.308
2006 Impact Factor 3.846
2005 Impact Factor 2.812
2004 Impact Factor 2.866
2003 Impact Factor 3.214
2002 Impact Factor 2.867
2001 Impact Factor 1.841
2000 Impact Factor 1.897
1999 Impact Factor 1.788
1998 Impact Factor 1.583
1997 Impact Factor 1.143
1996 Impact Factor 0.89
1995 Impact Factor 1.182
1994 Impact Factor 1.124
1993 Impact Factor 1.349
1992 Impact Factor 1.571

Impact factor over time

Impact factor

Additional details

5-year impact 3.75
Cited half-life 9.40
Immediacy index 0.77
Eigenfactor 0.01
Article influence 1.06
ISSN 1872-6216

Publisher details


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    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Psychological stress may be an important extrinsic factor which influences aging process. However, neither study demonstrated the mechanism by which chronic stress participates in skin aging. Aim of this study was to investigate the effects of chronic psychological stress on mice skin. Mice were daily submitted to rotational stress, for 28 days, until euthanasia. After 28 days, mice were killed and normal skin was analyzed. Macroscopically, dorsum skin of chronically stressed mice presented more wrinkled when compared to that of nonstressed mice. In mice skin, chronic stress increased lipid peroxidation, carbonyl protein content, nitrotyrosine levels, neutrophil infiltration, neutrophil elastase, tissue inhibitor of metalloproteinase-1 and metalloproteinase-8 levels. Nevertheless, chronic stress reduced dermis thickness, collagen type I, fibrilin-1 and elastin protein levels in mice skin. In in vitro assays, murine skin fibroblasts were exposed to elevated epinephrine levels plus inhibitors of reactive oxygen species (ROS) and reactive nitrogen species (RNS), fibroblast activity was evaluated in a short time. In skin fibroblast culture, treatment with inhibitors of ROS and RNS synthesis abolished the increase in carbonyl protein content and lipid peroxide accumulation induced by epinephrine. In conclusion, chronic psychological stress may be an important extrinsic factor, which contributes to skin aging in mice.
    Mechanisms of ageing and development 11/2015; 152. DOI:10.1016/j.mad.2015.10.004
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    ABSTRACT: Multiple isoforms of voltage-gated Na(+) channels (NaChs) have been identified in sinoatrial node (SAN) and contribute to a rapid intrinsic heart rate. However, their roles in aging remain unclear. Here, we sought to clarify whether the age-related expression of NaChs contributes to the impaired SAN function during aging. Blockade of the tetrodotoxin (TTX)-sensitive Na(+) current with nanomolar concentrations of TTX prolonged the cycle length (CL) in both the rat intact heart and SAN. The effect of nanomolar concentrations of TTX on SAN pacemaking was lessened in adulthood compared with that in youth. Interestingly, the pacemaking became more sensitive to TTX and TTX-induced sinus arrhythmias occurred more frequently in the senescent group. The presences of NaCh α subunit isoforms Nav1.1, Nav1.6 as well as β subunit isoforms Navβ1 and Navβ3 in SAN were confirmed by immunohistochemistry. Western blot revealed a declination of Nav1.1, Nav1.6, Navβ1 and Navβ3 proteins during aging. Furthermore, laser captured SAN cells were used for further real-time quantitative RT-PCR analysis, which also confirmed the presences of Nav1.1, Nav1.6, Navβ1 and Navβ3 mRNA and their reduced levels in rat SAN during aging. These results indicated an age-dependent alterations in expression and relative function of NaCh in rat SAN.
    Mechanisms of ageing and development 11/2015; DOI:10.1016/j.mad.2015.10.003
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    ABSTRACT: Aging is conditioned by genetic and environmental factors. Hyperphosphatemia is related to some pathologies, affecting to vascular cells behavior. This work analyze whether high concentration of extracellular phosphate induces vascular smooth muscle cells senescence, exploring the intracellular mechanisms and highlighting the in vivo relevance of this phenomenon. Human aortic smooth muscle cells treated with β-Glycerophosphate (BGP, 10mM) suffered cellular senescence by increasing p53, p21 and p16 expression and the senescence associated β-galactosidase activity. In parallel, BGP induced ILK overexpression, dependent on the IGF-1 receptor activation, and oxidative stress. Down-regulating ILK expression prevented BGP-induced senescence and oxidative stress. Aortic rings from young rats treated with 10mM BGP for 48hours, showed increased p53, p16 and ILK expression and SA-β-gal activity. Seven/eight nephrectomized rats feeding a hyperphosphatemic diet and fithteen- month old mice showed hyperphosphatemia and aortic ILK, p53 and p16 expression. In conclusion, we demonstrated that high extracellular concentration of phosphate induced senescence in cultured smooth muscle through the activation of IGF-1 receptor and ILK overexpression and provided solid evidences for the in vivo relevance of these results since aged animals showed high levels of serum phosphate linked to increased expression of ILK and senescence genes.
    Mechanisms of ageing and development 10/2015; 152. DOI:10.1016/j.mad.2015.10.001
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    ABSTRACT: Considering the crucial pathogenic role of CD4+ T cells in experimental autoimmune encephalomyelitis (EAE) and the opposite direction of the sexual dimorphism in the severity of the disease in 22-24- and 3-month-old Dark Agouti rats, sex differences in CD4+ T-cell-mediated immune response in aged rats immunized for EAE were examined and compared with those in young animals. In the inductive phase of EAE, fewer activated CD4+ lymphocytes were retrieved from draining lymph nodes of male (developing less severe disease) compared with female rats, due, at least partly, to their lesser expansion. The former reflected a greater suppressive capacity of CD4+CD25+Foxp3+ cells. Consequently, CD4+ lymphocyte infiltration into the spinal cord of aged male rats was diminished. At the peak of EAE, the frequency of reactivated cells was lower, whereas that of the regulatory CD4+ cells was higher in male rat spinal cord. Consistently, microglial activation and the expression of proinflammatory/damaging cytokines in male rat spinal cord mononuclear cells were diminished. Additionally, the frequency of the highly pathogenic IFN-γ+IL-17+T lymphocytes infiltrating their spinal cord was lower. Together, these results point to (i) an age-specificity in CD4+ cell-mediated immune response and (ii) mechanisms underlying the sex differences in this response in aged rats.
    Mechanisms of ageing and development 09/2015; 152. DOI:10.1016/j.mad.2015.09.004
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    ABSTRACT: Human cytomegalovirus (CMV), the prototypical β-herpervirus, is a widespread pathogen that establishes a lifelong latent infection in myeloid progenitor, and possibly other cells as well. Although immunocompetent individuals show mild or no symptoms despite periodic reactivation during myeloid cell differentiation, CMV is responsible for considerable morbidity and mortality in older adults and in persons chronically infected with HIV. Indeed, in these individuals, reactivation of CMV can cause serious complications. This review will focus of the effects of CMV during aging and HIV/AIDS, with particular attention to the cellular immunity and age-related pathology outcomes from this persistent infection. The impact of the long-term chronic exposure to CMV antigens on the expansion of CD8 T cells with features of replicative senescence will be highlighted.
    Mechanisms of ageing and development 09/2015; DOI:10.1016/j.mad.2015.09.003
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    ABSTRACT: The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions.
    Mechanisms of ageing and development 09/2015; 152. DOI:10.1016/j.mad.2015.09.002
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    ABSTRACT: Retinoids (vitamin A and its derivatives) are critical for a spectrum of developmental and physiological processes, in which steroid hormones also play indispensable roles. The StAR protein predominantly regulates steroid biosynthesis in steroidogenic tissues. We reported that regulation of retinoid, especially atRA and 9-cis RA, responsive StAR transcription is largely mediated by an LXR-RXR/RAR heterodimeric motif in the mouse StAR promoter. Herein we demonstrate that retinoids are capable of enhancing StAR protein, P-StAR, and steroid production, in granulosa, adrenocortical, glial, and epidermal cells. Whereas transient expression of RARα and RXRα enhanced 9-cis RA-treated StAR gene transcription, silencing of RXRα with siRNA, decreased StAR and steroid levels. An oligonucleotide probe encompassing an LXR-RXR/RAR motif bound to adrenocortical and epidermal keratinocyte NEs in EMSAs. ChIP studies revealed association of RARα and RXRα with the StAR proximal promoter. Further studies demonstrated that StAR mRNA levels decreased in diseased and elderly men and women skin tissues and that atRA could restore steroidogenesis in epidermal keratinocytes of aged individuals. These findings provide novel insights into the relevance of retinoid signaling in the up-regulation of steroid biosynthesis in various target tissues, and indicate that retinoid therapy may have important implications in age-related complications and diseases. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Mechanisms of ageing and development 08/2015; 150. DOI:10.1016/j.mad.2015.08.007
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    ABSTRACT: Alzheimer's disease is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological and clinical studies demonstrated that type 2 diabetes mellitus is an important risk factor for the development of Alzheimer's disease, i.e. the patients with type 2 diabetes mellitus are frequently companied with Alzheimer's disease symptoms. Despite many studies recently probed into the comorbid state of both diseases, so far the precise mechanism for this association is poorly understood. Emerging evidences suggest that defects in galanin play a central role on type 2 diabetes mellitus and is considered to be a risk factor for Alzheimer's disease development. This review provides a new insight into the multivariate relationship among galanin, type 2 diabetes mellitus and Alzheimer's disease, highlighting the effect of galanin system on the cross-talk between both diseases in human and rodent models. The current data support that activating central GalR2 attenuates insulin resistance and Alzheimer's disease feature in animal models. These may help us better understanding the pathogenesis of both diseases and provide useful hints for the development of novel therapeutic approaches to treat type 2 diabetes mellitus and Alzheimer's disease. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Mechanisms of ageing and development 08/2015; 150. DOI:10.1016/j.mad.2015.08.001
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    ABSTRACT: AGEs are posttranslational modifications generated by irreversible non-enzymatic crosslinking reactions between sugars and proteins - a reaction referred to as glycation. Glycation, a feature of ageing, can lead to non-degradable and less functional proteins and enzymes and can additionally induce inflammation and further pathophysiological processes such as neurodegeneration. In this study we investigated the influence of glycation on the high affinity NGF-receptor TrkA and the AGE-receptor RAGE. We quantified the binding affinity of the TrkA-receptor and RAGE to their ligands by surface plasmon resonance (SPR) and compared these to the binding affinity after glycation. At the same time, we established a glycation procedure using SPR. We found that glycation of TrkA reduced the affinity to NGF by a factor of three, which could be shown to lead to a reduction of NGF-dependent neurite outgrowth in PC12 cells. Glycation of RAGE reduced binding affinity of AGEs by 10-fold. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Mechanisms of ageing and development 07/2015; 150. DOI:10.1016/j.mad.2015.07.003
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    ABSTRACT: MARK-AGE aims at the identification of biomarkers of human aging capable of discriminating between the chronological age and the effective functional status of the organism. To achieve this, given the structure of the collected data, a proper statistical analysis has to be performed, as the structure of the data are non trivial and the number of features under study is near to the number of subjects used, requiring special care to avoid overfitting. Here we described some of the possible strategies suitable for this analysis. We also include a description of the main techniques used, to explain and justify the selected strategies. Among other possibilities, we suggest to model and analyze the data with a three step strategy. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Mechanisms of ageing and development 07/2015; 151. DOI:10.1016/j.mad.2015.07.001
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    ABSTRACT: In Alzheimer's disease (AD), activated microglia invade and surround β-amyloid plaques, possibly contributing to the aggregation of amyloid β (Aβ), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD. In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk (2, 6, or 18mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze tasks, and significantly improved learning and memory function in the Morris water maze (MWM) tasks. In addition, yonk reduced the area of Aβ plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PS1 mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX(+) cells compared to vehicle-treated transgenic mice. These results suggest that yonk could rescue cognitive deficits by ameliorated amyloid burden through regulating APP processing, inhibited the over-activation of microglia and astrocytes as well as restored neurogenesis. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Mechanisms of ageing and development 07/2015; 150. DOI:10.1016/j.mad.2015.07.002