2026-05-05T12:30:21Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/450192025-01-29T10:04:41Zcom_10324_44585com_10324_954com_10324_894col_10324_44586

Río Lorenzo, Alba del Rojo Ruiz, Jonatan Alonso Alonso, María Teresa García-Sancho Martín, Francisco Javier Producción Científica 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. 2021-01-15 2021-01-15 2020 info:eu-repo/semantics/article Journal of Cell Science, 2020, vol. 133, n. 6. 9 p. 1477-9137 http://uvadoc.uva.es/handle/10324/45019 10.1242/jcs.240879 eng https://jcs.biologists.org/content/133/6/jcs240879 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ © 2020 The Company of Biologists Attribution-NonCommercial-NoDerivatives 4.0 Internacional The Company of Biologists