Search results for " STRESS"
showing 10 items of 3936 documents
Paradoxical effect of l-arginine: Acceleration of endothelial cell senescence
2009
We have recently shown that inhibition of nitric oxide (NO) synthesis by asymmetrical dimethylarginine (ADMA) accelerated endothelial cell (EC) senescence which was prevented by coincubation with L-arginine; however the effect of long-term treatment of l-arginine alone on senescence of ECs have not been investigated. Human ECs were cultured in medium containing different concentrations of L-arginine until senescence. L-Arginine paradoxically accelerated senescence indicated by inhibiting telomerase activity. Moreover, L-arginine decreased NO metabolites, increased peroxynitrite, and 8-iso-prostaglandin F(2alpha) formation. In old cells, the mRNA expression of human amino acid transporter (h…
Overexpression of apolipoprotein J in human fibroblasts protects against cytotoxicity and premature senescence induced by ethanol and tert-butylhydro…
2008
Human diploid fibroblasts (HDFs) exposed to subcytotoxic stresses under H2O2, tert-butylhydroperoxide (t-BHP), and ethanol (EtOH) undergo stress-induced premature senescence (SIPS) characterized by many biomarkers of HDFs replicative senescence. Among these biomarkers are a growth arrest, an increase in the senescence-associated β-galactosidase activity, a senescent morphology, an overexpression of p21waf-1 and the subsequent inability to phosphorylate pRb, the presence of the common 4977-bp mitochondrial deletion, and an increase in the steady-state level of several senescence-associated genes such as apolipoprotein J (apo J). Apo J has been described as a survival gene against cytotoxic s…
Oxidative Stress and the Epigenetics of Cell Senescence: Insights from Progeroid Syndromes.
2019
Background: Cell senescence constitutes a critical process to respond to a variety of insults and adverse circumstances. Senescence involves the detention of DNA replication and cell proliferation, and hence, genetic programs associated with DNA damage response, chromosome stability, chromatin rearrangement, epigenetic reprogramming, and cell cycle are tightly linked to the senescent phenotype. Although senescence increases with age, the real implication of senescence regulation in the progress of aging in humans is largely discussed. In this context, reactive oxygen species (ROS) accumulation has also been postulated to play a critical role in cell homeostasis, aging processes, and contro…
Telomere length and cardiovascular disease
2010
SummaryTelomeres are structures composed of deoxyribonucleic acid repeats that protect the end of chromosomes, but shorten with each cell division. They have been the subject of many studies, particularly in the field of oncology, and more recently their role in the onset, development and prognosis of cardiovascular disease has generated considerable interest. It has already been shown that these structures may deteriorate at the beginning of the atherosclerotic process, in the onset and development of arterial hypertension or during myocardial infarction, in which their length may be a predictor of outcome. As telomere length by its nature is a marker of cell senescence, it is of particula…
The dual role of p53: DNA protection and antioxidant.
2011
The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer. However, more recently it has been show that p53 is not only involved in cancer, but also in ageing. p53 is stimulated by stress, which in turn results in the activation of a wide range of transcriptional targets. Low-intensity stress will activate p53 in a manner which results in antioxidant response, thus protecting against ageing because of its antioxidant function. On the contrary, high-intensity activation of p53 will re…
Regulation of the p19(Arf)/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice.
2015
Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the stud…
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy.
2013
Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3). Although therapy-induced senescence (TIS) improves long-term outcomes, potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Eµ-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h1 to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but …
Long-term effects of delayed parenthood.
1998
The present study aims to define, characterize and compare the long-term effects on offspring of delayed parenthood. Data published so far on this topic show that maternal and paternal ageing may affect offspring by different mechanisms. Delayed motherhood is characterized by increased probability of obstetric complications and/or fetal and perinatal problems which, in turn, may increase the risks of mortality and morbidity in newborns and later life. Furthermore, maternal ageing is distinguished by a decreased ratio of male to female infants and higher odds of conceiving a trisomic child and/or an individual suffering from mitochondrial DNA disorders. In contrast, delayed fatherhood is ass…
The importance of culturing primary cells under physiological conditions: proliferation, senescence, pluripotency
2017
Mesenchymal stem cells (MSCs), such as human dental pulp stem cells (hDPSCs), are currently a source for cell therapy. However, cell therapy protocols require 10–400 million cells per treatment, and consequently, they need to be expanded in vitro before implantation, with the inconvenience that MSCs undergo senescence following a certain number of cell expansion passages, loosing their stem cell qualities. Ambient oxygen tension (21% pO2) is normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% pO2. We previously demonstrated that hDPSC proliferation rate is significantly lowered at 21% pO2 due to enhanced oxidative stress, which led to the activation …
The role of mitochondrial oxidative stress in aging.
2003
Mitochondria are both a major source of oxidants and a target for their damaging effects, and, therefore, mitochondrial oxidative stress appears to be a cause, rather than a consequence, of cell aging. Oxidative damage in aging is particularly high in specific molecular targets, such as mitochondrial DNA and aconitase, and mitochondrial oxidative stress may drive tissue aging through intrinsic apoptosis. Mitochondrial function and morphology are impaired upon aging, as judged by a decline in membrane potential as well as by an increase in peroxide production and size of the organelles. In view of the age-related decreases in mitochondrial protein synthesis, mitochondrial transcripts, and ex…