The post-mitotic cell reached by normal cell populations after serial divisions has been regarded as the hallmark of cell senescence. It was proposed that this non-dividing cell is a mechanism of protection against malignant transformation and different approaches have been used to induce the post-mitotic state. There are contradictions and ...

Skin cancers and extrinsic aging are delayed consequences of cumulative UV radiation insults. Exposure of human keratinocytes to UVB has been previously shown to trigger premature senescence. In order to explore the involvement of the cyclin-dependent kinase inhibitor p16(INK-4a) in UVB-induced premature senescence, we developed an original model of repeated ...

Phospholipase D (PLD) has been implicated in mitotic regulation and has been shown to be defective in cells following replicative senescence. We examined the source of changes in PLD activity in senescent human umbilical vein endothelial cells and in human diploid fibroblasts. Using fractionated cell components we found that the ...

Aim: To determine whether transcriptional reprogramming is capable of reversing the developmental aging of normal human somatic cells to an embryonic state. Materials & methods: An isogenic system was utilized to facilitate an accurate assessment of the reprogramming of telomere restriction fragment (TRF) length of aged differentiated cells to that ...

Senescence is increasingly recognized as a critical feature of mammalian cells to suppress tumorigenesis, acting together with cell death programs. Whether senescence, like programmed cell death, can be exploited therapeutically has been unclear. Pandolfi and coworkers now propose that PTEN-loss-induced cellular senescence (PICS) may be triggered in vivo for therapy.

On the basis of the extension reaction of a telomerase substrate (TS) primer in the presence of the telomerase, the inherent signal-transduction mechanism of the hairpin fluorescence probe, and the strand-displacement property of polymerase, an amplified fluorescence detection of telomerase activity in the cancer cells was described in this manuscript. ...

Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumors. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells ...

In normal somatic cells, telomere length shortens with each cell replication. This progressive shortening is associated with cellular senescence and apoptosis. Germ cells, stem cells, and the majority of cancer cells express telomerase, an enzyme that extends telomere length and, when expressed at sufficient levels, can immortalize or extend the ...

Mitotic cells in culture show a limited replicative potential and after extended subculturing undergo a terminal growth arrest termed cellular senescence. When cells reach the senescent phenotype, this is accompanied by a significant change in the cellular phenotype and massive changes in gene expression, including the upregulation of secreted factors. ...

Aging is one of the most basic properties of living organisms. Abundant evidence supports the idea that cell senescence underlies organismal aging in higher mammals. Therefore, examining the molecular mechanisms that control cell and replicative senescence is of great interest for biology and medicine. Several discoveries strongly support telomere shortening ...

Presently, there is growing interest on telomerase activity in all cells (somatic cells, stem cells, cancerous cells and others) since this activity is associated with cellular changes such as proliferation, differentiation, immortalization, cell injury and ageing. Telomerase activity is absent in most of the somatic cells but present in over ...

Immortal bovine mammary epithelial cell lines are useful for providing an efficient indicator for transgene expression and for technology improvement of genetic modification. The preparation of hTERT-mediated immortalized mammary epithelial cells (MECs) requires a downregulation of p16INK4a. Here, we report the establishment of two immortal bovine MECs by expression of ...

Lysosomes are a cell organelle type processing antimicrobial activity. Here, we investigate the lysosomal activity in a primary cell line, bovine aortic endothelial cells (BAECs), during cellular aging, based on the antimicrobial activity of lysosomes isolated from BAECs at cell passages 4, 6, 8, and 10. Cytochemical analysis of lysosomes ...

Reprogramming of adult differentiated cells to a more pluripotent state has been achieved by various means, including somatic cell nuclear transfer (SCNT) and, more recently, by over expression of specific transcription factors to generate the so-called induced pluripotent stem (iPS) cells. Since telomeres play an important role in the maintenance ...

In this issue of Blood, Ugel and colleagues provide evidence that, in murine models, telomerase is an efficient target for adoptive cell therapy against a variety of cancer cells, but also can elicit an autoimmune response against B cells.(1).

Cellular senescence is an irreversible growth arrest and is presumed to be a natural barrier to tumor development. Like telomere shortening, certain defects in chromosome integrity can trigger senescence, however, the roles of centromere proteins in regulating commitment to the senescent state remains to be established. We examined chromatin structure ...

An optical fiber nanobiosensor was constructed to successfully detect a general cancer biomarker, telomerase at single cell level with its nanoscale tip. The nanotip immobilized with a specific antibody was inserted into a MCF-7 breast cancer cell nucleus to capture telomerases directly, after which an in vitro enzymatic sandwich immunoassay ...

In Epstein-Barr virus (EBV) negative Hodgkin's cell lines and classical EBV-negative Hodgkin's lymphoma (HL), Reed-Sternberg cells (RS cells) represent end-stage tumor cells, in which further nuclear division becomes impossible because of sustained telomere loss, shortening and aggregation. However, the three-dimensional (3D) telomere organization in latent membrane protein 1 (LMP1)-expressing RS ...

Genetic material in the nucleus governs mechanisms related to cell proliferation, differentiation, and function. Thus, senescence and aging are directly tied to the change of nuclear function and structure. The most important mechanisms that affect cell senescence are: (i) telomere shortening; (ii) environmental stress-mediated accumulation of DNA mutations, and (iii) ...

Terminally differentiated cell types are needed to live and function in a postmitotic state for a lifetime. Cellular senescence is another type of permanent arrest that blocks the proliferation of cells in response to genotoxic stress. Here we show that the retinoblastoma protein (pRB) uses a mechanism to block DNA ...

OBJECTIVE: Recent reports have shown that multipotent stem cells/progenitor cells that are capable of proliferation and regeneration are present in mammalian cochleae. However, progenitor cells have not been isolated from the adult cochlea. We examined the proliferative potential of cells derived from neonatal rats of various ages. The determination of ...

Werner syndrome (WS) results from defects in the gene encoding WRN RecQ helicase. WS fibroblasts undergo premature senescence in culture. Because cellular senescence is a tumor suppressor mechanism, we examined whether WS fibroblasts exhibited reduced tumorigenicity, in comparison to control cells, in a model of experimental conversion of normal human ...

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the synthesis of prostaglandins. Its overexpression induces numerous tumor-promoting phenotypes and is associated with cancer metastasis and poor clinical outcome. Although COX-2 inhibitors are promising chemotherapeutic and chemopreventative agents for cancer, the risk of significant cardiovascular and gastrointestinal complications currently outweighs their potential ...

We investigated the pathologic significance of ductular reactions in chronic liver diseases with respect to cellular senescence. The expression of senescence-associated markers (p16(INK4a) and p21(WAF1/Cip1)), cell proliferation, cell cycle markers (cyclin D and cyclin A), and neural cell adhesion molecule (NCAM) was examined immunohistochemically in primary biliary cirrhosis (PBC, n ...

The telomeric complex, shelterin, plays a critical role in protecting chromosome ends from erosion, and disruption of these complexes can lead to chromosomal instability culminating in cell death or malignant transformation. We reported previously that dominant-negative mutants of one of the telomeric proteins called TIN2 causes death of androgen receptor ...

Propagation of a species requires periodic cell renewal to avoid clonal senescence. Liu et al. (2010) now describe a new mechanism of cell renewal in budding yeast, in which damaged protein aggregates are transported out of the daughter buds along actin cables to preserve youthfulness.

Summary Elderly individuals have an increased susceptibility to microbial infections due to age-related anatomical, physiological, and environmental factors. However, the mechanism of aging-dependent susceptibility to infection is not fully understood. Here, we found that caveolae-dependent endocytosis is elevated in senescent cells. Thus, we focused on the implications of caveolae-dependent endocytosis ...

Summary Telomerase is a reverse transcriptase specialized in telomere synthesis. The enzyme is primarily nuclear where it elongates telomeres but many reports show that the catalytic component of telomerase (in humans called hTERT) also localizes outside of the nucleus, including in mitochondria. Shuttling of hTERT between nucleus and cytoplasm and ...

OBJECTIVE: To investigate the alterations in microRNA (miRNA) expression during replicative senescence (RS) in human trabecular meshwork (HTM) cells. METHODS: Two HTM cell lines were serially passaged until they reached replicative senescence. Changes in expression of 30 miRNAs were assessed by TaqMan real-time Q-PCR. Effects of miR-146a on gene expression ...

The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem ...

Expression of the human HIN-200 family member IFI 16 has been reported to suppress cell growth and contribute to the onset of cellular senescence. However the molecular events involved in this process have not been fully characterised. We fused IFI 16 to the estrogen receptor ligand-binding domain to establish an ...

Senescence is a general cellular process that occurs as a response to stress and damage. It forms an alternative response of cells to damage that might otherwise cause programmed cell death. Whereas telomere shortening leading to telomere dysfunction was the first described cause of senescence, it is now known that ...

This study aims to demonstrate the role of stress-induced senescence in aged-related neointimal formation. We demonstrated that aging increases senescence-associated beta-galactosidase activity (SA-beta-Gal) after vascular injury and the subsequent neointimal formation (neointima-to-media ratio: 0.8 +/- 0.2 vs. 0.54 +/- 0.15) in rats. We found that senescent cells (SA-beta-Gal(+) p21(+)) were ...

Crude extract of Scutellaria baicalensis (S. baicalensis) has cytotoxic effect on human myelogenous leukemia cells (HL-60). We invesigated which compound from the crude extract is responsible for the cytotoxic effect on HL-60 cells. We identified 29 compounds from the crude extract using high performance liquid chromatography mass spectrometry (HPLC/MS). Two ...

Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard ...

BACKGROUND: Senescent cells are well-recognized in the aging/degenerating human disc. Senescent cells are viable, cannot divide, remain metabolically active and accumulate within the disc over time. Molecular analysis of senescent cells in tissue offers a special challenge since there are no cell surface markers for senescence which would let one ...

The anti-aging effects of cyanidin were investigated under stress-induced premature senescence (SIPS) using WI-38 human diploid fibroblasts. WI-38 cells that were treated with 300 microM H(2)O(2) showed losses of cell viability, increased lipid peroxidation, and shortened cell lifespans. However, treatment with cyanidin attenuated cellular oxidative stress through increase of cell ...

ABSTRACT: Senescence and mitotic catastrophe (MC) are two distinct crucial non-apoptotic mechanisms, often triggered in cancer cells and tissues in response to anti-cancer drugs. Chemotherapeuticals and myriad other factors induce cell eradication via these routes. While senescence drives the cells to a state of quiescence, MC drives the cells towards ...

Cellular senescence--the permanent arrest of cycling in normally proliferating cells such as fibroblasts--contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and ...

Cellular senescence is an extremely stable form of cell cycle arrest activated in response to stress. Autophagy, a lysosome-dependent cellular catabolic process, can also be triggered by cellular stresses. Both senescence and autophagy have been implicated in a similar range of pathophysiologies, including cancer, aging and age-related symptoms. Senescence is ...

Background: Alveolar cell senescence is accelerated in patients with chronic obstructive pulmonary disease (COPD). Objectives: We tested the hypothesis that alveolar cell senescence contributes to the chronic inflammation that affects the lungs of COPD patients. Methods: We exposed alveolar type II-like epithelial (A549) cells to a G-quadruplex-interacting telomerase inhibitor in ...

Embryonal tumours most commonly occur in the first few years of life and account for approximately 30% of childhood malignancies. Knowledge of these tumours' genetics has already impacted on their clinical management and further knowledge of their cellular immortalization will hopefully result in novel therapies. The ends of human chromosomes ...

Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 ...

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. METHODS: ...

Telomerase is a ribonucleoprotein complex. It consists of two main components, human telomerase reverse transcriptase (hTERT) and human telomerase RNA. High telomerase activity is present in most malignant cells, but it is barely detectable in majority of somatic cells. The direct correlation between telomerase reactivation and carcinogens has made hTERT ...

Large cell change involves the clustering of hepatocytes with hyperchromatism and cellular enlargement without an increase in the nuclear/cytoplasmic ratio. This study investigated whether large cell change in chronic viral hepatitis reflects cellular senescence because of morphological similarities between the 2 conditions. The expression of markers of senescence such as ...

Cardiac tissue engineering will remain only a prospect unless large numbers of therapeutic cells can be provided, either from small samples of cardiac cells or from stem cell sources. In contrast to most adult cells, cardiomyocytes are terminally differentiated and cannot be expanded in culture. We explored the feasibility of ...

Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is ...

Agents stabilizing G-quadruplexes have the potential to destroy the functional structure of telomere and could therefore act as antitumor agents. We previously reported that SYUIQ-5 could stabilize G-quadruplex, induce senescence, and inhibit c-myc gene promoter activity. In this study, we showed that SYUIQ-5 inhibited proliferation of CNE2 and HeLa cancer ...

Ameloblastoma (AM) is recognized as a benign tumour but locally invasive with a high risk of recurrence. In vitro model systems for studying AM are limited due to the fact that AM cells grow poorly and begin to senesce early. Japanese researchers have reported the construction of an AM cell ...