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Dos reguladores epigenéticos conservados previenen el envejecimiento saludable

Jie Yuan1,2, Si-Yuan Chang1,2, Shi-Gang Yin3,2,4

  • 1Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

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Resumen

Los científicos descubrieron un mecanismo epigenético que regula negativamente el envejecimiento saludable. Esto implica genes específicos que, cuando se alteran, pueden prevenir el deterioro relacionado con la edad y mejorar la vida útil de los organismos modelo.

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Área de la Ciencia:

  • Epigenética y envejecimiento
  • La neurociencia
  • La genética

Sus antecedentes:

  • La esperanza de vida mundial ha aumentado, pero la salud no ha mejorado proporcionalmente.
  • Comprender las bases biológicas del envejecimiento saludable es crucial.
  • La esperanza de vida y la esperanza de vida saludable se pueden disociar, lo que pone de relieve la necesidad de estudiar los mecanismos de envejecimiento saludable.

Objetivo del estudio:

  • Identificar los mecanismos epigenéticos conservados que regulan el envejecimiento saludable.
  • Investigar los genes que modulan el deterioro del comportamiento relacionado con la edad.
  • Explorar posibles objetivos terapéuticos para promover el envejecimiento saludable.

Principales métodos:

  • Interferencia de ARN en todo el genoma (RNAi) en *Caenorhabditis elegans* para identificar genes que afectan el deterioro del comportamiento relacionado con la edad.
  • Investigó el papel de los reguladores epigenéticos específicos (BAZ-2 y SET-6) en C. elegans.
  • Los resultados validados en neuronas de ratón y células humanas cultivadas, y las bases de datos humanas y modelos de ratón examinados.

Principales resultados:

  • Se identificaron 59 genes que modulan el deterioro del comportamiento relacionado con la edad en C. elegans.
  • Descubrieron que los reguladores epigenéticos neuronales BAZ-2 y SET-6 aceleran el envejecimiento al deteriorar la función mitocondrial.
  • Se ha demostrado que los ortólogos humanos (BAZ2B, EHMT1) aumentan con la edad y se correlacionan con la progresión de la enfermedad de Alzheimer; la ablación *Baz2b* en ratones previene el deterioro cognitivo y el aumento de peso no saludable.

Conclusiones:

  • Un mecanismo epigenético conservado que involucra a BAZ-2 y SET-6 regula negativamente el envejecimiento saludable.
  • Estos reguladores epigenéticos afectan la función mitocondrial y están relacionados con el deterioro cognitivo relacionado con la edad.
  • Los resultados sugieren objetivos potenciales para las intervenciones destinadas a promover el envejecimiento saludable y a prolongar la vida útil.