Mitotic misregulation and human aging.

@article{Ly2000MitoticMA,
  title={Mitotic misregulation and human aging.},
  author={Danith H. Ly and David J. Lockhart and Richard A. Lerner and Peter G. Schultz},
  journal={Science},
  year={2000},
  volume={287 5462},
  pages={
          2486-92
        }
}
Messenger RNA levels were measured in actively dividing fibroblasts isolated from young, middle-age, and old-age humans and humans with progeria, a rare genetic disorder characterized by accelerated aging. Genes whose expression is associated with age-related phenotypes and diseases were identified. The data also suggest that an underlying mechanism of the aging process involves increasing errors in the mitotic machinery of dividing cells in the postreproductive stage of life. We propose that… 
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79 References

Replicative Senescence: Implications for in Vivo Aging and Tumor Suppression

Normal cells have limited proliferative potential in culture, a fact that has been the basis of their use as a model for replicative senescence for many years, and results indicate that multiple levels of control contribute to the irreversible growth arrest.

Progeria: a human-disease model of accelerated aging.

    W. Brown
    Biology, Medicine
    The American journal of clinical nutrition
  • 1992
It is hypothesize that the failure of patients with progeria to thrive may be due to a bioinactive form of GH and a lack of vasculogenesis caused by excess HA, a key gene with a major effect on normal aging.

Gene expression profile of aging and its retardation by caloric restriction.

Transcriptional patterns of calorie-restricted animals suggest that caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage.

A genome-wide transcriptional analysis of the mitotic cell cycle.

Molecular Biology of Aging

Polo-like kinases: positive regulators of cell division from start to finish.

    E. Nigg
    Biology
    Current opinion in cell biology
  • 1998

Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation.

The results clearly indicate that, if health status and biopsy conditions are controlled, the replicative lifespan of fibroblasts in culture does not correlate with donor age.

Alzheimer Presenilins in the Nuclear Membrane, Interphase Kinetochores, and Centrosomes Suggest a Role in Chromosome Segregation

Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia

Polo kinase: the choreographer of the mitotic stage?

The extension of identity beyond the catalytic domain strongly suggests that members of another conserved serine/threonine kinase family appears to be able to control the dynamics of cellular architecture and whether the polo-like kinases of different organisms have equivalent biological functions.
...