Telomere length and telomerase activity are related with immortalization frequency but not with replicative senescence in mammalian embryonic fibroblasts, except human embryonic fibroblasts

2014 ◽  
Vol 18 (6) ◽  
pp. 387-393 ◽  
Author(s):  
Hyun-Seok Kim ◽  
Jae-Seung Hong
Keyword(s):  
Telomere Length ◽  
Replicative Senescence ◽  
Telomerase Activity ◽  
Embryonic Fibroblasts ◽  
Human Embryonic Fibroblasts

Epigenetic features in regulation of telomeres and telomerase in stem cells

2021 ◽  
Author(s):  
Fatma Dogan ◽  
Nicholas R. Forsyth
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Cell Biology ◽  
Replicative Senescence ◽  
Telomerase Activity ◽  
Cell Phenotype ◽  
Tissue Degeneration ◽  
Unique System ◽  
Telomerase Regulation

The epigenetic nature of telomeres is still controversial and different human cell lines might show diverse histone marks at telomeres. Epigenetic modifications regulate telomere length and telomerase activity that influence telomere structure and maintenance. Telomerase is responsible for telomere elongation and maintenance and is minimally composed of the catalytic protein component, telomerase reverse transcriptase (TERT) and template forming RNA component, telomerase RNA (TERC). TERT promoter mutations may underpin some telomerase activation but regulation of the gene is not completely understood due to the complex interplay of epigenetic, transcriptional, and posttranscriptional modifications. Pluripotent stem cells (PSCs) can maintain an indefinite, immortal, proliferation potential through their endogenous telomerase activity, maintenance of telomere length, and a bypass of replicative senescence in vitro. Differentiation of PSCs results in silencing of the TERT gene and an overall reversion to a mortal, somatic cell phenotype. The precise mechanisms for this controlled transcriptional silencing are complex. Promoter methylation has been suggested to be associated with epigenetic control of telomerase regulation which presents an important prospect for understanding cancer and stem cell biology. Control of down-regulation of telomerase during differentiation of PSCs provides a convenient model for the study of its endogenous regulation. Telomerase reactivation has the potential to reverse tissue degeneration, drive repair, and form a component of future tissue engineering strategies. Taken together it becomes clear that PSCs provide a unique system to understand telomerase regulation fully and drive this knowledge forward into aging and therapeutic application.

scholarly journals Telomere Length, Telomerase Activity, and Replicative Potential in HIV Infection: Analysis of CD4+ and CD8+T Cells from HIV-discordant Monozygotic Twins

1997 ◽  
Vol 185 (7) ◽  
pp. 1381-1386 ◽  
Author(s):  
Larry D. Palmer ◽  
Nan-ping Weng ◽  
Bruce L. Levine ◽  
Carl H. June ◽  
H. Clifford Lane ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Telomere Length ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Replicative Senescence ◽  
Monozygotic Twins ◽  
Telomerase Activity ◽  
Replicative Capacity

To address the possible role of replicative senescence in human immunodeficiency virus (HIV) infection, telomere length, telomerase activity, and in vitro replicative capacity were assessed in peripheral blood T cells from HIV+ and HIV− donors. Genetic and age-specific effects on these parameters were controlled by studying HIV-discordant pairs of monozygotic twins. Telomere terminal restriction fragment (TRF) lengths from CD4+ T cells of HIV+ donors were significantly greater than those from HIV− twins. In contrast, telomere lengths in CD8+ T cells from HIV+ donors were shorter than in HIV− donors. The in vitro replicative capacity of CD4+ cells from HIV+ donors was equivalent to that of HIV− donors in response to stimulation through T cell receptor CD3 and CD28. Little or no telomerase activity was detected in freshly isolated CD4+ or CD8+ lymphocytes from HIV+ or HIV− donors, but was induced by in vitro stimulation of both HIV+ and HIV− donor cells. These results suggest that HIV infection is associated with alterations in the population dynamics of both CD4+ and CD8+ T cells, but fail to provide evidence for clonal exhaustion or replicative senescence as a mechanism underlying the decline in CD4+ T cells of HIV-infected donors.

scholarly journals New Function of CDC13 in Positive Telomere Length Regulation

2001 ◽  
Vol 21 (13) ◽  
pp. 4233-4245 ◽  
Author(s):  
Bettina Meier ◽  
Lucia Driller ◽  
Sigrun Jaklin ◽  
Heidi M. Feldmann
Keyword(s):  
Telomere Length ◽  
Protein Interactions ◽  
Replicative Senescence ◽  
Synthetic Lethality ◽  
State Level ◽  
Telomerase Activity ◽  
Regulatory Function ◽  
Protein Protein Interactions ◽  
New Mutation

ABSTRACT Two roles for the Saccharomyces cerevisiae Cdc13 protein at the telomere have previously been characterized: it recruits telomerase to the telomere and protects chromosome ends from degradation. In a synthetic lethality screen with YKU70, the 70-kDa subunit of the telomere-associated Yku heterodimer, we identified a new mutation in CDC13, cdc13-4, that points toward an additional regulatory function of CDC13. AlthoughCDC13 is an essential telomerase component in vivo, no replicative senescence can be observed in cdc13-4 cells. Telomeres of cdc13-4 mutants shorten for about 150 generations until they reach a stable level. Thus, incdc13-4 mutants, telomerase seems to be inhibited at normal telomere length but fully active at short telomeres. Furthermore, chromosome end structure remains protected in cdc13-4mutants. Progressive telomere shortening to a steady-state level has also been described for mutants of the positive telomere length regulator TEL1. Strikingly, cdc13-4/tel1Δ double mutants display shorter telomeres than either single mutant after 125 generations and a significant amplification of Y′ elements after 225 generations. Therefore CDC13, TEL1, and the Yku heterodimer seem to represent distinct pathways in telomere length maintenance. Whereas several CDC13 mutants have been reported to display elongated telomeres indicating that Cdc13p functions in negative telomere length control, we report a new mutation leading to shortened and eventually stable telomeres. Therefore we discuss a key role of CDC13 not only in telomerase recruitment but also in regulating telomerase access, which might be modulated by protein-protein interactions acting as inhibitors or activators of telomerase activity.

scholarly journals On the comparative biology of mammalian telomeres: Telomere length co-evolves with body mass and lifespan

2020 ◽  
Author(s):  
Michael Le Pepke ◽  
Dan Eisenberg
Keyword(s):  
Telomere Length ◽  
Body Mass ◽  
Dna Sequences ◽  
Replicative Senescence ◽  
Telomerase Activity ◽  
Sensitivity Analyses ◽  
Inverse Association ◽  
Mammal Species ◽  
Data Set ◽  
Telomere Biology

Telomeres, the short repetitive DNA sequences that cap the ends of linear chromosomes, shorten during cell division and are implicated in senescence in most species. The enzyme telomerase can rebuild telomeres but is repressed in many mammals that exhibit replicative senescence, presumably as a tumor suppression mechanism. It is therefore important that we have an accurate understanding of the (co-)evolution of telomere biology and life-history traits that has shaped the diversity of senescence patterns across species. Gomes et al. (2011) produced a large data set on telomere length (TL), telomerase activity, body mass and lifespan among 57 mammal species. We re-analyzed their data set using the same phylogenetic multiple regressions presented in the original publication and several sensitivity analyses. We found substantial inconsistencies in our results compared to Gomes et al.'s. Consistent with Gomes et al. we found an inverse association between TL and lifespan. Contrary to the analyses reported in Gomes et al., we found that there was a generally robust inverse association between TL and mass, and only weak non-robust evidence for an association between telomerase activity and mass. These results suggest that shorter TL may have been selected for in larger and longer-lived species – likely as a mechanism to suppress cancer. However, our results call into question past results suggesting that high telomerase activity has been selected against in larger species and stress the need for careful attention to model construction and sensitivity analyses.

Protein modification and replicative senescence of WI-38 human embryonic fibroblasts

Aging Cell ◽  
2010 ◽  
Vol 9 (2) ◽  
pp. 252-272 ◽  
Author(s):  
Emad K. Ahmed ◽  
Adelina Rogowska-Wrzesinska ◽  
Peter Roepstorff ◽  
Anne-Laure Bulteau ◽  
Bertrand Friguet
Keyword(s):  
Protein Modification ◽  
Replicative Senescence ◽  
Embryonic Fibroblasts ◽  
Human Embryonic Fibroblasts

scholarly journals Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tsung-Po Lai ◽  
Mark Simpson ◽  
Krunal Patel ◽  
Simon Verhulst ◽  
Jungsik Noh ◽  
...  
Keyword(s):  
Dna Damage ◽  
Preterm Birth ◽  
Telomere Length ◽  
Human Placenta ◽  
Replicative Senescence ◽  
Preterm Births ◽  
Full Term ◽  
Cellular Aging ◽  
Telomere Dysfunction ◽  
Replicative Aging

AbstractRecent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.

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