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Related Experiment Videos

Clonal attenuation in chick embryo fibroblasts. Experimental data, a model and computer simulations.

J C Angello, J W Prothero

    Cell and Tissue Kinetics
    |January 1, 1985
    PubMed
    Summary

    Cellular aging, or clonal attenuation, occurs as stem cells become committed to limited divisions. This process, modeled by a probability of commitment (Pc), explains declining cell proliferation in cultures over time.

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    Area of Science:

    • Cell Biology
    • Aging Research
    • Developmental Biology

    Background:

    • Fibroblast cultures exhibit variable clone sizes at low densities.
    • Clone size distribution correlates with the number of population doublings in mass cultures.

    Purpose of the Study:

    • To analyze the phenomenon of 'clonal attenuation' in cell cultures.
    • To develop and validate a mathematical model for clonal attenuation.

    Main Methods:

    • Development of a stochastic model based on cell commitment.
    • Computer simulations to analyze model parameters and outcomes.
    • Sensitivity analysis of model parameters.

    Main Results:

    • A model where stem cells commit to limited divisions explains clonal attenuation.

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  • The probability of commitment (Pc) increases exponentially with stem cell divisions.
  • A best-fit value of N=7 for obligatory divisions before terminal differentiation was determined.
  • Stem cell numbers increase initially, then decline rapidly as Pc exceeds 0.5, leading to senescence.

    • Conclusions:

    • The proposed model accurately describes clonal attenuation in fibroblast cultures.
    • Cell commitment is a key mechanism driving replicative senescence.
    • The model provides insights into stem cell dynamics and culture lifespan.