Similar Datasets
Project description:Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in ageing and are targets of DNA damage and DNA damage response. Although short telomeres have been implicated in heart failure, little is known about the role of telomeres in cardiomyocytes.To fill this gap in knowledge, we studied myocardial ageing in the form of telomere lengths under isogenic background.
2023-12-31 | GSE230455 | GEO
Project description:Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in ageing and are targets of DNA damage and DNA damage response. Although short telomeres have been implicated in heart failure, little is known about the role of telomeres in cardiomyocytes.To fill this gap in knowledge, we studied myocardial ageing in the form of telomere lengths under isogenic background.
2023-12-31 | GSE217702 | GEO
Project description:Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in ageing and are targets of DNA damage and DNA damage response. Although short telomeres have been implicated in heart failure, little is known about the role of telomeres in cardiomyocytes.To fill this gap in knowledge, we studied myocardial ageing in the form of telomere lengths under isogenic background.
2023-12-31 | GSE217701 | GEO
Project description:The number of (TTAGGG)n repeats at the ends of chromosomes is highly variable between individual chromosomes, between different cells and between species. Progressive loss of telomere repeats limits the proliferation of pre-malignant human cells but also contributes to aging by inducing apoptosis and senescence in normal cells. Despite enormous progress in understanding distinct pathways that result in loss and gain of telomeric DNA in different cell types, many questions remain. Further studies are needed to delineate the role of damage to telomeric DNA, replication errors, chromatin structure, liquid-liquid phase transition, telomeric transcripts (TERRA) and secondary DNA structures such as guanine quadruplex structures, R-loops and T-loops in inducing gains and losses of telomere repeats in different cell types. Limitations of current telomere length measurements techniques and differences in telomere biology between species and different cell types complicate generalizations about the role of telomeres in aging and cancer. Here some of the factors regulating the telomere length in embryonic and adult cells in mammals are discussed from a mechanistic and evolutionary perspective.
| S-EPMC9289283 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-07-01 | E-GEOD-58222 | biostudies-arrayexpress
Project description:AimsTelomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGF?) signalling pathway where inhibiting TGF? signalling maintains telomere length. The relationship between Pim1 and TGF? has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGF? signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.Methods and resultsTelomere length was maintained by lentiviral-mediated overexpression of PIM1 and inhibition of TGF? signalling in A549 cells. Telomere length maintenance was further demonstrated in isolated cardiomyocytes from mice with cardiac-specific overexpression of PIM1 and by pharmacological inhibition of TGF? signalling. Mechanistically, Pim1 inhibited phosphorylation of Smad2, preventing its translocation into the nucleus and repressing expression of TGF? pathway genes.ConclusionPim1 maintains telomere lengths in cardiomyocytes by inhibiting phosphorylation of the TGF? pathway downstream effectors Smad2 and Smad3, which prevents repression of telomerase reverse transcriptase. Findings from this study demonstrate a novel mechanism of telomere length maintenance and provide a potential target for preserving cardiac function.
| S-EPMC7797214 | biostudies-literature
Project description:Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients with treatment-resistant depression (TRD, 125 with major depressive disorder, MDD, and 23 with bipolar disorder, BD) treated with electroconvulsive therapy (ECT) and analyzed whether LTL was associated with different response profiles. We also compared LTL between patients with TRD and 335 non-psychiatric controls. For 107 patients for which genome-wide association data were available, we evaluated whether a significant overlap among genetic variants or genes associated with LTL and with response to ECT could be observed. LTL was negatively correlated with age (Spearman's correlation coefficient = -0.25, p < 0.0001) and significantly shorter in patients with treatment-resistant MDD (Quade's F = 35.18, p < 0.0001) or BD (Quade's F = 20.84, p < 0.0001) compared to controls. Conversely, baseline LTL was not associated with response to ECT or remission. We did not detect any significant overlap between genetic variants or genes associated with LTL and response to ECT. Our results support previous findings suggesting premature cell senescence in patients with severe psychiatric disorders and suggest that LTL could not be a predictive biomarker of response to ECT.
| S-EPMC8622097 | biostudies-literature
Project description:To examine the established link between DNA replication and telomere length, we tested whether firing of telomeric origins would cause telomere lengthening. We found that RIF1 mutants that block Protein Phosphatase 1 (PP1) binding activated telomeric origins but did not elongate telomeres. In a second approach, we found overexpression of ?N-Dbf4 and Cdc7 increased DDK activity and activated telomeric origins, yet telomere length was unchanged. We tested a third mechanism to activate origins using the sld3-A mcm5-bob1 mutant that de-regulates the pre-replication complex, and again saw no change in telomere length. Finally, we tested whether mutations in RIF1 that cause telomere elongation would affect origin firing. We found that neither rif1-?1322 nor rif1HOOK affected firing of telomeric origins. We conclude that telomeric origin firing does not cause telomere elongation, and the role of Rif1 in regulating origin firing is separable from its role in regulating telomere length.
| S-EPMC7371424 | biostudies-literature
Project description:Telomeres are DNA repeats at the ends of linear chromosomes and are replicated by telomerase, a ribonucleoprotein reverse transcriptase. Telomere length regulation and chromosome end capping are essential for genome stability and are mediated primarily by the shelterin and CST complexes. POT1-TPP1, a subunit of shelterin, binds the telomeric overhang, suppresses ATR-dependent DNA damage response, and recruits telomerase to telomeres for DNA replication. POT1 localization to telomeres and chromosome end protection requires its interaction with TPP1. Therefore, the POT1-TPP1 complex is critical to telomere maintenance and full telomerase processivity. The aim of this mini-review is to summarize recent POT1-TPP1 structural studies and discuss how the complex contributes to telomere length regulation. In addition, we review how disruption of POT1-TPP1 function leads to human disease.
| S-EPMC7385035 | biostudies-literature
Project description:Yeast telomeres are anchored at the nuclear envelope (NE) through redundant pathways that require the telomere-binding factors yKu and Sir4. Significant variation is observed in the efficiency with which different telomeres are anchored, however, suggesting that other forces influence this interaction. Here, we show that subtelomeric elements and the insulator factors that bind them antagonize the association of telomeres with the NE. This is detectable when the redundancy in anchoring pathways is compromised. Remarkably, these same conditions lead to a reduction in steady-state telomere length in the absence of the ATM-kinase homologue Tel1. Both the delocalization of telomeres and reduction in telomere length can be induced by targeting of Tbf1 or Reb1, or the viral transactivator VP16, to a site 23 kb away from the TG repeat. This correlation suggests that telomere anchoring and a Tel1-independent pathway of telomere length regulation are linked, lending a functional significance to the association of yeast telomeres with the NE.
| S-EPMC1383557 | biostudies-literature