vol. 133 no. 6, jcs240879.
cover JCS


Alba Delrio-Lorenzo, Jonathan Rojo-Ruiz, María Teresa Alonso, Javier García-Sancho


Sarcopenia, the loss of muscle mass and strength associated with age, has been linked to impairment of the cytosolic Ca2+ peak that triggers muscle contraction, but mechanistic details remain unknown. Here we explore the hypothesis that a reduction in sarcoplasmic reticulum (SR) Ca2+ concentration ([Ca2+]SR) is at the origin of this loss of Ca2+ homeostasis. We engineered Drosophila melanogaster to express the Ca2+ indicator GAP3 targeted to muscle SR, and we developed a new method to calibrate the signal into [Ca2+]SR in vivo [Ca2+]SR fell with age from ∼600 µM to 50 µM in close correlation with muscle function, which declined monotonically when [Ca2+]SR was <400 µM. [Ca2+]SR results from the pump-leak steady state at the SR membrane. However, changes in expression of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump and of the ryanodine receptor leak were too modest to explain the large changes seen in [Ca2+]SR. Instead, these changes are compatible with increased leakiness through the ryanodine receptor as the main determinant of the [Ca2+]SR decline in aging muscle. In contrast, there were no changes in endoplasmic reticulum [Ca2+]with age in brain neurons.


El envejecimiento está asociado a una pérdida de masa y fuerza muscular, un fenómeno denominado sarcopenia. En este trabajo hemos investigado si el ión calcio, esencial para la contracción muscular, podría estar desregulado en este proceso. Esto se ha abordado en un modelo in vivo de envejecimiento en Drosophila. Nuestra conclusión es que el contenido del calcio del retículo sarcoplásmico disminuye según las moscas van envejeciendo y esto se correlaciona bien con el desarrollo de la sarcopenia.


 Group picture


Nuestro grupo, dirigido por Javier García-Sancho y Mª Teresa Alonso, centra su investigación en el Ca2+ subcelular y las señales generadas por organelas que acumulan Ca2+, como el retículo sarco-endoplásmico o la mitocondria. Para ello utilizamos distintos abordajes, desde la generación de nuevos sensores proteicos de Ca2+, hasta su aplicación al estudio de distintas funciones fisiopatológicas in vivo.

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