scholarly journals Telomere Length Reprogramming in Embryos and Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Keri Kalmbach ◽  
LeRoy G. Robinson ◽  
Fang Wang ◽  
Lin Liu ◽  
David Keefe
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Genetic Mutations ◽  
Subsequent Generation ◽  
Linear Chromosome ◽  
Age Related ◽  
Early Embryos

Telomeres protect and cap linear chromosome ends, yet these genomic buffers erode over an organism’s lifespan. Short telomeres have been associated with many age-related conditions in humans, and genetic mutations resulting in short telomeres in humans manifest as syndromes of precocious aging. In women, telomere length limits a fertilized egg’s capacity to develop into a healthy embryo. Thus, telomere length must be reset with each subsequent generation. Although telomerase is purportedly responsible for restoring telomere DNA, recent studies have elucidated the role of alternative telomeres lengthening mechanisms in the reprogramming of early embryos and stem cells, which we review here.

scholarly journals Spermatozoa telomeres determine telomere length in early embryos and offspring

Reproduction ◽  
2016 ◽  
Vol 151 (1) ◽  
pp. 1-7 ◽  
Author(s):  
C de Frutos ◽  
A P López-Cardona ◽  
N Fonseca Balvís ◽  
R Laguna-Barraza ◽  
D Rizos ◽  
...  
Keyword(s):  
Telomere Length ◽  
Mus Musculus ◽  
Mus Spretus ◽  
Cell Stage ◽  
Young Males ◽  
Early Embryos ◽  
Parent Of Origin ◽  
Telomere Lengthening ◽  
Zygote Stage

Offspring telomere length (TL) has been correlated with paternal TL, but the mechanism for this parent of origin-specific inheritance remains unclear. The objective of this study has been to determine the role of spermatozoa TL in embryonic telomere lengthening by using two mouse models showing dimorphism in their spermatozoa TL: Mus musculus vs Mus spretus and old vs young Mus musculus. Mus spretus spermatozoa displayed a shorter TL than Mus musculus. Hybrid offspring exhibited lower TL compared with Mus musculus starting at the two-cell stage, before the onset of telomerase expression. To analyze the role of spermatozoa telomeres in early telomere lengthening, we compared the TL in oocytes, zygotes, two-cell embryos and blastocysts produced by parthenogenesis or by fertilization with Mus musculus or Mus spretus spermatozoa. TL was significantly higher in spermatozoa compared with oocytes, and it increased significantly from the oocyte to the zygote stage in those embryos fertilized with Mus musculus spermatozoa, but not in those fertilized with Mus spretus spermatozoa or produced by parthenogenesis. A further increase was noted from the zygote to the two-cell stage in fertilized Mus musculus embryos, whereas hybrid embryos maintained the oocyte TL. Spermatozoa TL shortened with age in Mus musculus and the offspring from young males showed a significantly higher TL compared with that fathered by old males. These significant differences were already noticeable at the two-cell stage. These results suggest that spermatozoa telomeres act as a guide for telomerase-independent telomere lengthening resulting in differences in TL that persist after birth.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/151/1/1/suppl/DC1.

scholarly journals Telomeres, stem cells, and hematology

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1759-1766 ◽  
Author(s):  
Peter M. Lansdorp
Keyword(s):  
Stem Cells ◽  
Telomere Length ◽  
Cellular Response ◽  
Germ Line ◽  
Critical Role ◽  
Somatic Cells ◽  
Growth Stimulation ◽  
Critical Function ◽  
Telomere Attrition

Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal cells in which malignant progression is facilitated by genome instability resulting from uncapped telomeres. The critical role of telomeres in cell proliferation and aging is illustrated in patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Here, the role of telomeres and telomerase in human biology is reviewed from a personal historical perspective.

scholarly journals Telomeres and Longevity: A Cause or an Effect?

2019 ◽  
Vol 20 (13) ◽  
pp. 3233 ◽  
Author(s):  
Huda Adwan Shekhidem ◽  
Lital Sharvit ◽  
Eva Leman ◽  
Irena Manov ◽  
Asael Roichman ◽  
...  
Keyword(s):  
Telomere Length ◽  
Ongoing Debate ◽  
Telomere Attrition ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Extreme Longevity ◽  
Linear Chromosomes ◽  
Biological State

Telomere dynamics have been found to be better predictors of survival and mortality than chronological age. Telomeres, the caps that protect the end of linear chromosomes, are known to shorten with age, inducing cell senescence and aging. Furthermore, differences in age-related telomere attrition were established between short-lived and long-lived organisms. However, whether telomere length is a “biological thermometer” that reflects the biological state at a certain point in life or a biomarker that can influence biological conditions, delay senescence and promote longevity is still an ongoing debate. We cross-sectionally tested telomere length in different tissues of two long-lived (naked mole-rat and Spalax) and two short-lived (rat and mice) species to tease out this enigma. While blood telomere length of the naked mole-rat (NMR) did not shorten with age but rather showed a mild elongation, telomere length in three tissues tested in the Spalax declined with age, just like in short-lived rodents. These findings in the NMR, suggest an age buffering mechanism, while in Spalax tissues the shortening of the telomeres are in spite of its extreme longevity traits. Therefore, using long-lived species as models for understanding the role of telomeres in longevity is of great importance since they may encompass mechanisms that postpone aging.

scholarly journals Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity

Haematologica ◽  
2021 ◽  
Author(s):  
Amanda Amoah ◽  
Anja Keller ◽  
Ramiz Emini ◽  
Markus Hoenicka ◽  
Andreas Liebold ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Ex Vivo ◽  
The Elderly ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Elevated Activity ◽  
Human Hscs ◽  
Age Related Changes

In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSCs). We report increased frequencies of HSC, HPC and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSCs further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSCs upon aging. The frequency of human HSCs polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarisation of aged human HSCs with respect to Cdc42. Elevated activity of Cdc42 in aged HSCs thus contributed to age-related changes in HSCs. Xeno-transplants, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSCs. Aged HSCs treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSCs. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSCs, and similar to mice, this presents a likely possibility for attenuation of aging in human HSCs.

scholarly journals Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 89 ◽  
Author(s):  
Christian Bär ◽  
Maria A. Blasco
Keyword(s):  
Environmental Factors ◽  
Telomere Length ◽  
Therapeutic Targets ◽  
Therapeutic Strategies ◽  
Telomere Shortening ◽  
Age Related ◽  
Human Telomere ◽  
Linear Chromosomes ◽  
Telomere Erosion

Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself.

scholarly journals Retrotransposons in pluripotent stem cells

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Jingwen Wang ◽  
Junjiu Huang ◽  
Guang Shi
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Expression Patterns ◽  
Vital Role ◽  
Copy Numbers ◽  
Early Embryos ◽  
Low Levels ◽  
Genomic Locations

AbstractTransposable elements constitute about half of the mammalian genome, and can be divided into two classes: the class I (retrotransposons) and the class II (DNA transposons). A few hundred types of retrotransposons, which are dynamic and stage specific, have been annotated. The copy numbers and genomic locations are significantly varied in species. Retrotransposons are active in germ cells, early embryos and pluripotent stem cells (PSCs) correlated with low levels of DNA methylation in epigenetic regulation. Some key pluripotency transcriptional factors (such as OCT4, SOX2, and NANOG) bind retrotransposons and regulate their activities in PSCs, suggesting a vital role of retrotransposons in pluripotency maintenance and self-renewal. In response to retrotransposons transposition, cells employ a number of silencing mechanisms, such as DNA methylation and histone modification. This review summarizes expression patterns, functions, and regulation of retrotransposons in PSCs and early embryonic development.

scholarly journals Alternative Lengthening of Telomeres (ALT) in Tumors and Pluripotent Stem Cells

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1030 ◽  
Author(s):  
Shuang Zhao ◽  
Feng Wang ◽  
Lin Liu
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
Telomere Length ◽  
Dna Sequences ◽  
Pluripotent Stem Cells ◽  
Telomerase Activity ◽  
Age Related ◽  
Alternative Lengthening ◽  
Damage Response ◽  
Length Regulation

A telomere consists of repeated DNA sequences (TTAGGG)n as part of a nucleoprotein structure at the end of the linear chromosome, and their progressive shortening induces DNA damage response (DDR) that triggers cellular senescence. The telomere can be maintained by telomerase activity (TA) in the majority of cancer cells (particularly cancer stem cells) and pluripotent stem cells (PSCs), which exhibit unlimited self-proliferation. However, some cells, such as telomerase-deficient cancer cells, can add telomeric repeats by an alternative lengthening of the telomeres (ALT) pathway, showing telomere length heterogeneity. In this review, we focus on the mechanisms of the ALT pathway and potential clinical implications. We also discuss the characteristics of telomeres in PSCs, thereby shedding light on the therapeutic significance of telomere length regulation in age-related diseases and regenerative medicine.

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