Search results for " senes"
showing 10 items of 146 documents
Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging
2005
Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences of age-associated cellular alterations on the biochemistry of APP processing have not been studied in molecular detail so far. Here, we report that processing of endogenous APP is down-regulated during the aging of normal human fibroblasts (IMR-90). The generation of intracellular APP cleavage products C99, C83, and AICD gradually declines with increasing life span and is accompanied by a reduced secretion of soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in senescent cells, which has been shown to be directly mediated by a…
B cell immunosenescence: different features of naive and memory B cells in elderly.
2011
Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/naive B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-10, and presence of somatic hypermutation, focusing on the IgG(+)IgD(-)CD27(-) double negative (DN) B cells that are expanded in the elderly. Our results show that naive B cells from young donors need a sufficiently strong stimulus to be activated "in vitro", while naive B cells from old subjects are able t…
Potential effects of age-associated oxidative stress on mammalian oocytes/embryos
1996
This bioessay aims to explain the different effects of maternal ageing and postovulatory oocyte ageing on mammalian oocytes/embryos under the scope of 'the oxygen radical-mitochondrial injury hypothesis of ageing'. This hypothesis assumes a key role in the senescent process of oxygen radical damage to mitochondrial DNA, proteins and lipids. It is proposed that a decrease in intracellular ATP concentrations and glutathione (GSH)/glutathione disulphide (GSSG) ratio together with a concomitant increase in cytosolic Ca2+ are major factors causing the observed detrimental effects of ageing on cytoskeletal fibres, fertilization and embryo development.
Role of p16INK4a and BMI-1 in oxidative stress-induced premature senescence in human dental pulp stem cells
2017
Human dental pulp stem cells (hDPSCs) are a source for cell therapy. Before implantation, an in vitro expansion step is necessary, with the inconvenience that hDPSCs undergo senescence following a certain number of passages, loosing their stemness properties. Long-term in vitro culture of hDPSCs at 21% (ambient oxygen tension) compared with 3–6% oxygen tension (physiological oxygen tension) caused an oxidative stress-related premature senescence, as evidenced by increased β-galactosidase activity and increased lysil oxidase expression, which is mediated by p16INK4a pathway. Furthermore, hDPSCs cultured at 21% oxygen tension underwent a downregulation of OCT4, SOX2, KLF4 and c-MYC factors, w…
Correlation of Zinc with Oxidative Stress Biomarkers
2015
Hypertension and smoking are related with oxidative stress (OS), which in turn reports on cellular aging. Zinc is an essential element involved in an individual’s physiology. The aim of this study was to evaluate the relation of zinc levels in serum and urine with OS and cellular aging and its effect on the development of hypertension. In a Spanish sample with 1500 individuals, subjects aged 20–59 years were selected, whose zinc intake levels fell within the recommended limits. These individuals were classified according to their smoking habits and hypertensive condition. A positive correlation was found (Pearson’s C = 0.639
Double Negative (CD19+IgG+IgD-CD27-) B Lymphocytes: A New Insight from Telomerase in Healthy Elderly, in Centenarian Offspring, and in Alzheimer’s Di…
2014
Background: We have previously reported the increase of IgD-CD27- (Double Negative, DN) B cell population in the aged. These memory B cells have short telomeres and poor abilities to proliferate in vitro. Here, we investigated whether the low ability of DN B cells to proliferate depends on the expression levels of the CD307d and CD22 inhibitory receptors or whether DN B cells can proliferate and reactivate telomerase by the engagement of both innate and adaptive immune receptors. Methods: Phenotypic analyses were made by using flow cytometry. Quantitative analysis of telomerase activity was made by using a TRAP and a photometric enzyme immunoassay in young, healthy elderly, centenarian offs…
Activity of mannose-binding lectin in centenarians
2012
We analyzed MBL2 gene variants in two cohorts of centenarians, octo-nonagenarians and nonagenarians, and in the general population, one from Sardinia Island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. We also assessed in vitro the effect of mannose-binding lectin (MBL) on various human cells at different stage of senescence. The frequency of high and null activity haplotypes was significantly lower, and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population fro…
miR-126-3p and miR-21-5p as Hallmarks of Bio-Positive Ageing; Correlation Analysis and Machine Learning Prediction in Young to Ultra-Centenarian Sici…
2022
Human ageing can be characterized by a profile of circulating microRNAs (miRNAs), which are potentially predictors of biological age. They can be used as a biomarker of risk for age-related inflammatory outcomes, and senescent endothelial cells (ECs) have emerged as a possible source of circulating miRNAs. In this paper, a panel of four circulating miRNAs including miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p, involved in several pathways related to inflammation, and ECs senescence that seem to be characteristic of the healthy ageing phenotype. The circulating levels of these miRNAs were determined in 78 healthy subjects aged between 22 to 111 years. Contextually, extracellular miR-1…
Up-Regulation of leucocytes Genes Implicated in Telomere Dysfunction and Cellular Senescence Correlates with Depression and Anxiety Severity Scores
2012
BACKGROUND: Major depressive disorder (MDD) is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to eval…
YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING
2022
Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the e…