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Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
Replicative Cell Senescence02:15

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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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Techniques to Induce and Quantify Cellular Senescence
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Published on: May 1, 2017

Replicative stress, stem cells and aging.

Yaroslava Ruzankina1, Amma Asare, Eric J Brown

  • 1Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.

Mechanisms of Ageing and Development
|May 9, 2008
PubMed
Summary

Maintaining genome integrity during DNA synthesis is crucial for preventing premature aging. Failures in DNA repair and cell cycle checkpoints impact stem cell pools, accelerating age-related diseases.

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Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • DNA synthesis is a vulnerable cell cycle phase, prone to replication errors and fork collapse.
  • Genome integrity maintenance is vital for preventing premature age-related diseases.
  • Stem and progenitor cell pools are particularly sensitive to DNA damage and genome instability.

Purpose of the Study:

  • To investigate the link between genome maintenance, cell cycle checkpoints, and age-related disease onset.
  • To highlight the importance of preserving stem and progenitor cell pools for tissue renewal capacity.

Main Methods:

  • Review of genetically engineered mouse models with specific mutations (e.g., Terc(-/-), ATR(mKO), Ku86(-/-)).
  • Analysis of DNA damage response pathways and cell cycle regulation.
  • Examination of telomere shortening and its impact on replicative potential.

Main Results:

  • Genome maintenance failures (e.g., telomere shortening) degrade tissue renewal capacity.
  • Accelerated aging phenotypes are observed in models with compromised genome integrity.
  • Cell cycle checkpoints modulate the impact of DNA damage on stem cell exhaustion.

Conclusions:

  • Both DNA repair mechanisms and cell cycle checkpoints critically influence age-related disease onset.
  • These processes affect aging, at least partly, by impacting long-term stem and progenitor cell potential.
  • Preserving genome integrity in stem cells is essential for healthy aging and tissue regeneration.