Mechanisms of ageing and development

Publisher: Elsevier

Current impact factor: 3.40

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 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


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors pre-print on any website, including arXiv and RePEC
    • Author's post-print on author's personal website immediately
    • Author's post-print on open access repository after an embargo period of between 12 months and 48 months
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months
    • Author's post-print may be used to update arXiv and RepEC
    • Publisher's version/PDF cannot be used
    • Must link to publisher version with DOI
    • Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License
    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Genetic ablation of CuZn-superoxide dismutase (Sod1) in mice (Sod1−/− mice) leads to shortened lifespan with a dramatic increase in hepatocellular carcinoma and accelerated aging phenotypes, including early onset sarcopenia. To study the tissue specific effects of oxidative stress in the Sod1−/− mice, we generated mice that only express the human SOD1 gene specifically in the liver of Sod1−/− mice (Sod1−/−/hSOD1alb mice). Expression of hSOD1 in the liver of Sod1−/− mice improved liver function, reduced oxidative damage in liver, and partially restored the expression of several genes involved in tumorigenesis, which are abnormally expressed in the livers of the Sod1−/− mice. However, liver specific expression of hSOD1 did not prevent the loss of body weight and muscle mass and alterations in the structure of neuromuscular junctions. The expression of hSOD1 in the liver of Sod1−/− mice significantly improved the lifespan of Sod1−/− mice; however, the lifespan of the Sod1−/−/hSOD1alb mice was still significantly shorter than wild type mice.
    No preview · Article · Feb 2016 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy is best known as a mechanism involved in cellular recycling of biomolecules during periods of nutritional starvation. More recently, an additional function of autophagy emerged: the selective degradation of functionally impaired or surplus proteins, organelles and invading bacteria. With this function autophagy is integrated in a network of pathways involved in molecular and cellular quality control with a key impact on development and aging. Impairments in the autophagic machinery lead to accelerated aging and the development of diseases. Here we focus on the role of nonselective autophagy and mitophagy, the selective autophagic degradation of mitochondria, on aging and lifespan of biological systems.
    No preview · Article · Jan 2016 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite extensive research, neither the incidence nor the rate of progression of Alzheimer's disease (AD) has significantly changed. Some biochemical and genetic defects that initiate and promote AD include: (a) increased oxidative stress, (b) chronic inflammation (c) mitochondrial dysfunction, (d) Aß1-42 peptides generated from the amyloid precursor protein (APP), (e) proteasome inhibition, and (f) mutations in APP, presenilin-1 and presenilin-2 genes. Increased oxidative stress appears to precede other biochemical and genetic defects. Oxidative damage induces chronic inflammation. Therefore, reducing these defects simultaneously may reduce the development and progression of AD. Previous studies with individual antioxidants produced consistent benefits in animal models of AD; however, a similar approach produced inconsistent results in human AD. This review proposes a hypothesis that simultaneous elevation of the levels of antioxidant enzymes and antioxidant compounds is necessary for optimally reducing oxidative stress and chronic inflammation in human AD. Supplementation can enhance; but elevation of antioxidant enzymes requires activation of Nrf2. This review discusses activation and regulation of Nrf2. The need for multi- antioxidants that can affect multi-targets has been proposed without specific recommendations. This review proposes a micronutrient mixture that would simultaneously enhance the levels of antioxidant enzymes and antioxidant compounds in human AD.
    No preview · Article · Jan 2016 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    ABSTRACT: Substantial evidence suggests that chronic human cytomegalovirus (hCMV) infection contributes significantly to T-cell immunosenescence and adverse health outcomes in older adults. As such, it is important to search for compounds with anti-hCMV properties. Studies have shown that resveratrol, a sirtuin activator, suppresses hCMV infection. Here we report suppressive effects of sirtinol, a sirtuin antagonist, on hCMV infection and its cellular and molecular consequences. Human diploid fibroblast WI-38 cells were infected by hCMV Towne strain in the absence or presence of sirtinol. hCMV replication was measured using qPCR. Senescent phenotype was determined by senescence-associated β galactosidase (SA-β-Gal) activity. Expression of hCMV immediate early (IE) and early (E) proteins and senescence-associated proteins (pRb and Rb, p16(INK4), and p53) and production of reactive oxygen species (ROS) were assessed using standard laboratory assays. The results demonstrated that sirtinol suppressed hCMV infection as well as hCMV-induced activation of molecular mechanisms of senescence and ROS production. While underlying molecular mechanisms remain to be elucidated, these findings indicate sirtinol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection and its cellular and molecular consequences that are important to ageing and health of older adults.
    No preview · Article · Jan 2016 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 and latent CMV infection affect the frequency of NKT-like cells (CD8+CD56+T cells) and their response to Staphylococcal Enterotoxin B (SEB) in the context of CMV and ageing. NKT-like cell percentage increases with the combination of both CMV and age. The response to SEB and the polyfunctional index of NKT-like cells also increase with age in CMV-seropositive individuals. In young individuals, CMV infection induces a shift on the polyfunctional profile of CD8+CD56-T cells not observed on the NKT-like cells response. NKT-like cells expressing CD57 are expanded in CMV-seropositive individuals and are more polyfunctional than their CD57- counterpart. In addition CD57- NKT-like cells are more polyfunctional than CD8+CD56-CD57-T cells. The results support that the expansion of polyfunctional NKT-cells may have a beneficial effect on the immune response against pathogens.
    No preview · Article · Jan 2016 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    ABSTRACT: Immunosenescence involves age-related remodeling changes in the organization of lymphoid organs and functionality of immune cells, which have been associated with increased morbidity and mortality The pace of immunosenescence is modulated, however, by both intrinsic and extrinsic factors. Here, we review the mechanisms by which some factors, like the oxidative stress and certain chronic viral infections, may modulate the ageing immune system. Mounting evidence indicates that human cytomegalovirus (CMV) drives the expansion of late-differentiated T cells with an inflammatory profile. This would add to the “inflammaging” phenomenon, characterized by a low-grade inflammatory state, importantly involved in the etiology of several age-related diseases. We discuss that age-related oxidative stress is associated with chronic inflammation, and the oxidation-inflammation theory of ageing is summarized. According to this theory, the ageing process is a chronic oxidative and inflammatory stress, leading to damage of cell components, including proteins, lipids and DNA, and contributing to the age-related decline of physiological functions. Moreover oxi-inflamm-aging is associated with immunosenescence, which could be involved in the rate of ageing of individuals.
    No preview · Article · Jan 2016 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cyclosporine A (CsA) and tacrolimus (FK506) are the most important immunosuppressive compounds that block the activation of helper T-cells. In this study, we investigated the effects of CsA and FK506 on growth and senescence of articular chondrocytes. Chondrocytes from young rabbit cartilage entered senescence after 8.6 ± 0.8 population doublings (PDs), while chondrocytes treated with CsA and FK506 entered senescence after 12.3 ± 1.4 and 13.7 ±0.6 PDs, respectively. Furthermore, chondrocytes from the cartilage of old rabbits were senescent after 2.6 ± 0.9 PDs, whereas those treated with CsA and FK506 were senescent after 8.2 ± 1.8 and 6.9 ± 1.6 PDs, respectively. These compounds also inhibited senescence induction of chondrocytes in a high-cell density pellet culture system. We previously reported that p38MAPK plays a critical role in the onset of senescence in chondrocyte. This study revealed that the phosphorylation of p38MAPK was inhibited by either CsA or FK506. The early onset of senescence in chondrocyte harboring MKK6E, which is a constitutively-active form of MKK6 and increases p38MAPK phosphorylation, was blocked by CsA. These results suggest that CsA and FK506 increase the proliferation and inhibit the senescence of articular chondrocytes through inactivation of p38MAPK.
    No preview · Article · Dec 2015 · Mechanisms of ageing and development
  • [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.
    No preview · Article · Nov 2015 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Nov 2015 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Oct 2015 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Sep 2015 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Sep 2015 · Mechanisms of ageing and development
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Sep 2015 · Mechanisms of ageing and development