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La inhibición de la señalización de IL-11 prolonga la salud y la vida útil de los mamíferos
Anissa A Widjaja1, Wei-Wen Lim2,3, Sivakumar Viswanathan2
1Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. anissa.widjaja@duke-nus.edu.sg.
Nature
|July 17, 2024
Resumen
La interleucina-11 (IL-11), una citocina proinflamatoria, tiene un impacto negativo en el envejecimiento y la esperanza de vida. La inhibición de la IL-11 en ratones mejoró la esperanza de vida, redujo la fragilidad y prolongó significativamente la esperanza de vida.
Área de la Ciencia:
- Investigación sobre el envejecimiento y la longevidad
- Inmunología y inflamación
- Biología molecular y celular
Sus antecedentes:
- El envejecimiento se caracteriza por la inflamación y la disminución de la salud y la esperanza de vida.
- Las vías celulares clave como ERK, AMPK y mTORC1 son críticas en los procesos de envejecimiento.
- La citoquina proinflamatoria Interleucina-11 (IL-11) se regula hacia arriba con la edad.
Objetivo del estudio:
- Investigar el papel de la IL-11 en las enfermedades asociadas a la edad y la esperanza de vida.
- Para determinar si la IL-11 afecta negativamente la salud y la longevidad.
- Explorar el potencial terapéutico de la inhibición de la IL-11 en el envejecimiento.
Principales métodos:
- Se examinó la regulación de la IL-11 en ratones envejecidos.
- Utilizó la deleción genética de Il11 y Il11ra1 en ratones.
- Se administró terapia anti-IL-11 a ratones envejecidos.
- Se evaluó la función metabólica, la multi-morbilidad, la fragilidad y la esperanza de vida.
Principales resultados:
- La IL-11 está regulada al alza en ratones envejecidos y regula el eje ERK-AMPK-mTORC1.
- La eliminación de Il11 o Il11ra1 protege contra el deterioro y la fragilidad relacionados con la edad.
- El tratamiento anti-IL-11 mejoró el metabolismo, la función muscular y redujo los biomarcadores del envejecimiento.
- La deleción genética de IL-11 extendió la vida útil del ratón en un promedio de 24.9%.
- El tratamiento anti-IL-11 prolongó la esperanza de vida media tanto en ratones machos (22,5%) como en ratones hembras (25%).
Conclusiones:
- La citocina proinflamatoria IL-11 juega un papel importante en la salud y la esperanza de vida de los mamíferos.
- La inhibición de la IL-11 representa una estrategia terapéutica potencial para las patologías relacionadas con la edad.
- La terapia anti-IL-11, actualmente en ensayos clínicos para la fibrosis, puede ofrecer un enfoque traslacional para las intervenciones de envejecimiento.
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