Search results for "Telomere"

Telomeric length heterogeneity influences spontaneous regression of malignant melanoma

2016

Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

2019

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomer…

Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells

2021

© 2021 by the authors.

2019

By using all atom molecular dynamics simulations, we studied the behavior of human DNA telomere sequences in guanine quadruplex (G4) conformation and in the presence of oxidative lesions, namely abasic sites. In particular, we evidenced that while removing one guanine base induces a significant alteration and destabilization of the involved leaflet, human telomere oligomers tend, in most cases, to maintain at least a partial quadruplex structure, eventually by replacing the empty site with undamaged guanines of different leaflets. This study shows that (i) the disruption of the quadruplex leaflets induces the release of at least one of the potassium cations embedded in the quadruplex channe…

Longitudinal study of DNA methylation during the first 5 years of life

2016

[Background]: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. [Methods]: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects,…

Telomere length and physical performance among older people-The Helsinki Birth Cohort Study.

2019

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses stre…

Telomere Length and Frailty: The Helsinki Birth Cohort Study

2018

Objectives: Telomere length is associated with aging-related pathologies. Although the association between telomere length and frailty has been studied previously, only a few studies assessing longitudinal changes in telomere length and frailty exist. Design: Longitudinal cohort study. Setting and participants: A subpopulation of the Helsinki Birth Cohort Study consisting of 1078 older adults aged 67 to 79 years born in Helsinki, Finland, between 1934 and 1944. Measures: Relative leukocyte telomere length (LTL) was measured using quantitative real-time polymerase chain reaction at the average ages of 61 and 71 years, and at the latter the participants were assessed for frailty according to …

The Older Finnish Twin Cohort : 45 Years of Follow-up

2019

AbstractThe older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945–1957 in 2011–2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938–1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these …

Kinetic evidence for interaction of TMPyP4 with two different G-quadruplex conformations of human telomeric DNA

2018

Background: Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in> 80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence. Methods: UV–Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics. Results: TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show th…

Alternative lengthening of telomeres (ALT) influences survival in soft tissue sarcomas: a systematic review with meta-analysis

2019

Background Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic. Methods We searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- pati…