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Explorando el papel desconocido de la senescencia celular en enfermedades raras
Piera Selvaggio1, Esi Taci1,2, Alessandra Barassi1,3
1Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, Milano, Italy.
Orphanet journal of rare diseases
|September 2, 2025
Resumen
La senescencia celular, un proceso que implica la detención del ciclo celular y los cambios epigenéticos, está cada vez más relacionada con enfermedades raras. Esta revisión explora su papel en las cromatinopatías y enfermedades pulmonares, sugiriendo nuevos objetivos terapéuticos.
Área de la Ciencia:
- Biología celular y molecular
- Genética y Epigenética
- Investigación de las enfermedades raras
Sus antecedentes:
- La senescencia celular implica la detención del ciclo celular, las alteraciones epigenéticas y un fenotipo secretor asociado a la senescencia (SASP).
- La senescencia está implicada en procesos fisiológicos y patológicos, incluidos los síndromes progeroides raros.
- Su papel en enfermedades raras sin rasgos evidentes de envejecimiento sigue siendo en gran medida desconocido.
Objetivo del estudio:
- Revisar la participación de la senescencia celular en los trastornos mendelianos raros de la maquinaria epigenética (cromatinopatías) y las enfermedades pulmonares raras.
- Comprender cómo las alteraciones del epigenoma y las modificaciones del microambiente en la senescencia impulsan el inicio y la progresión de la enfermedad.
- Explorar la senescencia como un factor potencial en enfermedades raras que carecen de las características típicas del envejecimiento.
Principales métodos:
- Revisión de los conocimientos actuales sobre la senescencia en cuatro cromatinopatías: síndromes de Sotos, Cornelia de Lange, Rett y Kleefstra.
- Análisis de la participación de la senescencia en cuatro enfermedades pulmonares raras: fibrosis quística, fibrosis pulmonar idiopática, hipertensión arterial pulmonar y linfangioleiomiomatosis.
- Examen de la relación entre los defectos epigenéticos, SASP, y la progresión de la enfermedad en trastornos raros seleccionados.
Principales resultados:
- Las cromatinopatías exhiben defectos epigenéticos relacionados con las características de la senescencia.
- Las enfermedades pulmonares raras muestran la acumulación de células senescentes y un SASP proinflamatorio que juega un papel central.
- La senescencia contribuye a la aparición y progresión de la enfermedad a través de la alteración del epigenoma y la modificación del microambiente.
Conclusiones:
- Investigar la senescencia en diversas enfermedades raras mejora la comprensión de su papel en trastornos complejos.
- La senescencia surge como un nuevo jugador en la patogénesis de enfermedades raras.
- Esta investigación puede conducir a nuevos objetivos terapéuticos para enfermedades raras.
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