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Un cambio inducido por la edad a un estado de hiperrecombinación.

Michael A McMurray1, Daniel E Gottschling

  • 1Division of Basic Sciences, The Fred Hutchinson Cancer Research Center, and Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98109, USA.

Science (New York, N.Y.)
|September 27, 2003
PubMed
Resumen

A medida que las células de levadura envejecen, la inestabilidad genómica aumenta significativamente, indicada por un aumento de 100 veces en la pérdida de heterocigosidad (LOH). Esta inestabilidad genómica relacionada con la edad parece independiente de la extensión de la vida útil, lo que sugiere la inestabilidad inherente del genoma nuclear con el envejecimiento.

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Área de la Ciencia:

  • Genética La genética.
  • Biología celular Biología celular.
  • Gerontología Gerontología.

Sus antecedentes:

  • Existe una fuerte correlación entre el envejecimiento y el desarrollo del cáncer.
  • Los mecanismos subyacentes que vinculan el envejecimiento con el cáncer, particularmente la inestabilidad genómica, siguen siendo en gran medida desconocidos.
  • Comprender la inestabilidad genómica relacionada con la edad es crucial para la investigación del cáncer.

Objetivo del estudio:

  • Investigar la inestabilidad genómica como un sello distintivo del cáncer en relación con el envejecimiento celular.
  • Examinar la relación entre el envejecimiento y la pérdida de heterocigosidad (LOH) en Saccharomyces cerevisiae.

Principales métodos:

  • Se utilizaron células madre diploides de levadura (Saccharomyces cerevisiae) para modelar el envejecimiento celular.
  • Pérdida cuantificada de heterocigosidad (LOH) como medida de la inestabilidad genómica.
  • Comparación de la frecuencia y los mecanismos de la LOH en células jóvenes frente a células envejecidas.
  • Evaluó el impacto de la extensión de la esperanza de vida en la LOH inducida por la edad.

Principales resultados:

  • Se observó un aumento significativo de aproximadamente 100 veces en el LOH en el envejecimiento de las células madre diploides de levadura.
  • La aparición y la frecuencia de la LOH inducida por la edad no se vieron afectadas por la extensión de la vida útil, lo que sugiere un reloj de envejecimiento independiente.
  • Los mecanismos de LOH pasaron de la recombinación recíproca en células jóvenes a la recombinación no recíproca en células envejecidas, predominantemente en la progenie.

Conclusiones:

  • La inestabilidad genómica, específicamente LOH, aumenta sustancialmente con la edad celular en la levadura.
  • La LOH inducida por la edad parece seguir un reloj biológico distinto, no afectado por las intervenciones que extienden la vida útil.
  • Los hallazgos sugieren que los genomas nucleares pueden poseer inestabilidad inherente que se manifiesta con el aumento de la edad.