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El aumento de la señalización de Wnt durante el envejecimiento altera el destino de las células madre musculares y
Andrew S Brack1, Michael J Conboy, Sudeep Roy
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|August 11, 2007
Resumen
El envejecimiento perjudica la regeneración muscular al promover la fibrosis de las células madre. La activación de la señalización Wnt en las células madre musculares envejecidas impulsa esta conversión fibrogénica, sugiriéndola.
Área de la Ciencia:
- Gerontología y Medicina Regenerativa.
- Biología de las células madre Biología de las células madre
- Fisiología del músculo esquelético Fisiología del músculo esquelético
Sus antecedentes:
- La capacidad de regeneración del músculo esquelético disminuye con la edad avanzada.
- El aumento de la fibrosis tisular es un sello distintivo del deterioro muscular relacionado con la edad.
Objetivo del estudio:
- Investigar los mecanismos subyacentes a la disfunción de las células madre musculares relacionadas con la edad.
- Explorar el papel de la vía de señalización Wnt en el compromiso del linaje de células madre musculares durante el envejecimiento.
Principales métodos:
- Análisis comparativo de células madre musculares (células satélite) de ratones jóvenes y viejos.
- Evaluación de la conversión de linaje miogénico versus fibrogénico in vitro.
- Investigación de la activación canónica de la vía de señalización Wnt y su modulación por inhibidores de Wnt.
- Análisis de los factores séricos de ratones envejecidos y su interacción con los receptores de Frizzled.
Principales resultados:
- Las células madre musculares envejecidas exhiben una propensión a cambiar de linajes miogénicos a fibrógenos tras la proliferación.
- Esta conversión de linaje está mediada por factores sistémicos presentes en animales de edad avanzada.
- La activación de la vía de señalización canónica Wnt se observa en progenitores miogénicos envejecidos y se correlaciona con la fibrosis.
- Los inhibidores de Wnt pueden suprimir esta conversión de linaje relacionada con la edad.
- Los componentes específicos del suero de ratones envejecidos se unen a las proteínas de Frizzled, lo que podría conducir a una elevación de la señalización Wnt.
Conclusiones:
- La vía de señalización Wnt está involucrada críticamente en el envejecimiento de las células madre específicas de los tejidos.
- La desregulación de la señalización de Wnt contribuye al aumento de la fibrosis en el músculo esquelético envejecido.
- Dirigirse a la vía Wnt puede ofrecer estrategias terapéuticas para contrarrestar la degeneración muscular relacionada con la edad.
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