Endothelin-1 induces cellular senescence and fibrosis in cultured myoblasts. A potential mechanism of aging-related sarcopenia
Authors
Alcalde Estévez, Elena; Asenjo Bueno, Ana; Sosa Callejas, Patricia; Olmos Centenera, Gemma; Plaza Expósito, Patricia; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/58480DOI: 10.18632/aging.103450.
ISSN: 1945-4589
Date
2020-06-22Affiliation
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas; Universidad de Alcalá. Departamento de Biología de SistemasBibliographic citation
Aging, 2020, v. 12, n. 12, p. 11200-11223
Keywords
endothelin-1
fibrosis
senescence
aging
sarcopenia
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Endothelial dysfunction, with increased endothelin-1 (ET-1) synthesis, and sarcopenia, characterized by the loss of muscular mass and strength, are two aging-related conditions. However, a relationship between them has not been already established. The aim of this study was to determine whether ET-1 induces senescence and fibrosis in cultured murine myoblasts, which could be involved in the development of sarcopenia related to aging. For this purpose, myoblasts were incubated with ET-1 to assess cellular senescence, analyzed by senescence associated beta-galactosidase activity and p16 expression; and fibrosis, assessed by fibronectin expression. ET-1 induced myoblast senescence and fibrosis through ETA receptor. The use of antioxidants and several antagonists revealed that ET-1 effect on senescence and fibrosis depended on ROS production and activation of PI3K-AKT-GSK pathway. To stress the in vivo relevance of these results, circulating ET-1, muscular strength, muscular fibrosis and p16 expression were measured in male C57Bl6 mice from 5-18-24-months-old. Old mice shown high levels of ET-1 correlated with muscular fibrosis, muscular p16 expression and loss of muscle strength. In conclusion, ET-1 promotes fibrosis and senescence in cultured myoblasts, similar results were found in old mice, suggesting a potential role for ET-1 in the development of sarcopenia related to aging.
Files in this item
Files | Size | Format |
|
---|---|---|---|
Endothelin_Alcalde_Aging_2020.pdf | 2.581Mb |
|
Files | Size | Format |
|
---|---|---|---|
Endothelin_Alcalde_Aging_2020.pdf | 2.581Mb |
|
Collections
- FISIOLOG - Artículos [87]