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La restricción calórica promueve la supervivencia celular de los mamíferos mediante la inducción de la desacetilasa

Haim Y Cohen¹, Christine Miller, Kevin J Bitterman

¹Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Science (New York, N.Y.)

|June 19, 2004

Resumen

La restricción calórica (CR) puede extender la vida útil al aumentar la expresión Sir2 (SIRT1) de los mamíferos, que protege las células de la muerte. Esto implica que SIRT1 desacetila Ku70, impidiendo que el factor proapoptótico Bax llegue a las mitocondrias.

Área de la Ciencia:

Biología celular Biología celular.
Investigación sobre el envejecimiento de la investigación.
Los mecanismos moleculares del envejecimiento.

Sus antecedentes:

El envejecimiento está relacionado con la pérdida acumulativa de células.
La restricción calórica (CR) en la levadura retrasa el envejecimiento a través de la activación de Sir2.
Comprender los efectos de la CR en los mamíferos es crucial para la investigación del envejecimiento.

Objetivo del estudio:

Para investigar el papel de los mamíferos Sir2 (SIRT1) en la restricción calórica (CR).
Para dilucidar el mecanismo molecular por el cual SIRT1 influye en la supervivencia celular y el envejecimiento.

Principales métodos:

Medición de la expresión de SIRT1 en ratas y células humanas en condiciones de CR.
Investigando la interacción entre SIRT1, Ku70 y Bax.
Evaluación del efecto de SIRT1 en la apoptosis inducida por el estrés.

Principales resultados:

La expresión de SIRT1 es inducida por CR en ratas y células humanas.
La insulina y la señalización de IGF-1 atenuan la respuesta SIRT1 inducida por CR.
SIRT1 desacetila Ku70, lo que lleva al secuestro de Bax desde las mitocondrias.
Este proceso inhibe la muerte celular apoptótica inducida por el estrés.

Conclusiones:

CR prolonga la vida útil potencialmente mediante la regulación al alza de SIRT1.
SIRT1 promueve la supervivencia celular mediante la inhibición de la apoptosis.
La vía SIRT1-Ku70-Bax es un mediador clave de los efectos antienvejecimiento de la CR.

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