Search results for "TELOMERES"

Telomere length and physical performance at older ages:an individual participant meta-analysis

2013

<p>Background: Telomeres are involved in cellular ageing and shorten with increasing age. If telomere length is a valuable biomarker of ageing, then telomere shortening should be associated with worse physical performance, an ageing trait, but evidence for such an association is lacking. The purpose of this study was to examine whether change in telomere length is associated with physical performance.</p>\ud \ud <p>Methods: Using data from four UK adult cohorts (ages 53–80 years at baseline), we undertook cross-sectional and longitudinal analyses. We analysed each study separately and then used meta-analytic methods to pool the results. Physical performance was measured us…

Relative Telomere Length and Cardiovascular Risk Factors

2019

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status…

Acetylated nucleosome assembly on telomeric DNAs

2003

Abstract The role of histone N-terminal domains on the thermodynamic stability of nucleosomes assembled on several different telomeric DNAs as well as on ‘average’ sequence DNA and on strong nucleosome positioning sequences, has been studied by competitive reconstitution. We find that histone tails hyperacetylation favors nucleosome formation, in a similar extent for all the examined sequences. On the contrary, removal of histone terminal domains by selective trypsinization causes a decrease of nucleosome stability which is smaller for telomeres compared to the other sequences examined, suggesting that telomeric sequences have only minor interactions with histone tails. Micrococcal nuclease…

An Organometallic Gold(I) Bis‐N‐Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells

2020

Abstract The organometallic AuI bis‐N‐heterocyclic carbene complex [Au(9‐methylcaffeine‐8‐ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G‐quadruplex (G4) structures. This study sheds light on the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry‐based methods, including shotgun proteomics in A2780 ovarian cancer cells. In contrast to other metal‐based anticancer agents, this organogold compound is less prone to form coordinative bonds with biological nucleophiles and is expected to exert its drug effects mainly by non‐covalent interactions. Global protein expression changes of treated cancer cell…

The histone deacetylase Rpd3 regulates telomeric heterochromatin structure of polytene chromosomes

2010

The telomeric Cdc13-Stn1-Ten1 complex regulates RNA polymerase II transcription

2019

Advance article.

The role of telomeres and telomerase in the senescence of postmitotic cells

2020

Senescence is a process related to the stopping of divisions and changes leading the cell to the SASP phenotype. Permanent senescence of many SASP cells contributes to faster aging of the body and development of age-related diseases due to the release of pro-inflammatory factors. Both mitotically active and non-dividing cells can undergo senescence as a result of activation of different molecular pathways. Telomeres, referred to as the molecular clock, direct the dividing cell into the aging pathway when reaching a critical length. In turn, the senescence of postmitotic cells depends not on the length of telomeres, but their functionality. Dysfunctional telomeres are responsible for trigger…

Telomere dysfunction in cells with arsenic-induced genomic instability

2005

It is well known that the occurrence of dicentric chromosomes represent signature of telomere dysfunction and is a clear symptom of genomic instability. V79 Chinese hamster cells, treated with 10µM sodium arsenite for 24h and allowed to grow in drug-free medium (ASO cells), showed genomic instability with aneuploidy and nuclear abnormalities as well as the appearance of dicentric chromosomes since the 90th cell generation. TRAP assay was performed on growing ASO cells and on clones isolated during the course of the expanded growth. As expected, some clones with dicentric chromosomes and severely reduced telomerase activity went to death; surprisingly, other clones also bearing chromosomal e…

From cellular senescence to age-associated diseases: miRNAs as tools and targets for healthy ageing

2017

miRNAs are the most abundant RNA species to be found in cell-free blood, encapsulated within microvesicles or bound to proteins. miRNAs play essential roles in the regulation of various biological processes. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain age-related diseases. So, they might be an ideal target for modulating healthy ageing

Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence.

2020

Telomeres have the ability to adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomere chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a dis…