Convergent Early Dysregulation of Sarcopenia-Associated Genes in Skeletal Muscle During Aging and SOD1G93A ALS Models
6 affiliations
- 1LAGENBIO, Faculty of Veterinary, University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain
- 2Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, 28029 Madrid, Spain
- 3AgroFood Institute of Aragon (IA2), 50013 Zaragoza, Spain
- 4Institute of Health Research of Aragon (IIS), 50009 Zaragoza, Spain
- 5Laboratory Affiliated to Istituto Pasteur Italia—Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy
- 6Scuola Superiore di Studi Avanzati Sapienza (SSAS), Sapienza University of Rome, 00161 Rome, Italy
Abstract
Skeletal muscle undergoes structural and functional decline due to aging and neuromuscular disorders such as amyotrophic lateral sclerosis (ALS), both of which impact protein expression and contribute to muscle atrophy. This study investigates how aging and the SOD1G93A ALS-related mutation affect the expression of eight genes previously linked to sarcopenia (PF4, OIT3, MMRN1, MASP1, C1R, SVEP1, VCAN and SPTB) but not yet characterized in muscle tissue. To this end, we analyzed their expression (1) during muscle aging in WT mice (5 and 24 months), (2) in SOD1G93A-transfected myotube cells in vitro, (3) in a muscle-specific SOD1G93A mouse model (5 and 24 months), and (4) in a systemic SOD1G93A transgenic mouse at different disease stages (60 and 120 days) by quantitative PCR. All eight target genes were expressed in skeletal muscle and most of them showed increased transcription with aging. In ALS models, gene expression was significantly overexpressed at early stages, particularly in muscle-specific (MLC/SOD1G93A) and systemic (SOD1G93A) models, mimicking aging-related profiles. These alterations attenuated with disease progression, suggesting an early transient muscle response to ALS-linked SOD1 mutations. Hence, this study demonstrates that sarcopenia-associated proteins are actively expressed and modulated in skeletal muscle during aging and ALS and suggests convergent response mechanisms.
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BibTeX
@article{aparicio2026convergent,
title = {{Convergent Early Dysregulation of Sarcopenia-Associated Genes in Skeletal Muscle During Aging and SOD1G93A ALS Models}},
author = {Paula Aparicio and Gabriella Dobrowolny and Martina Lupoli and Laura Moreno-Martínez and Tresa López-Royo and Antonio Musarò and Raquel Manzano and Rosario Osta},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219529},
url = {https://www.mdpi.com/1422-0067/27/21/9529},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Convergent Early Dysregulation of Sarcopenia-Associated Genes in Skeletal Muscle During Aging and SOD1G93A ALS Models
AU - Paula Aparicio
AU - Gabriella Dobrowolny
AU - Martina Lupoli
AU - Laura Moreno-Martínez
AU - Tresa López-Royo
AU - Antonio Musarò
AU - Raquel Manzano
AU - Rosario Osta
PY - 2026
DA - 2026/10/25
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219529
UR - https://www.mdpi.com/1422-0067/27/21/9529
AB - Skeletal muscle undergoes structural and functional decline due to aging and neuromuscular disorders such as amyotrophic lateral sclerosis (ALS), both of which impact protein expression and contribute to muscle atrophy. This study investigates how aging and the SOD1G93A ALS-related mutation affect the expression of eight genes previously linked to sarcopenia (PF4, OIT3, MMRN1, MASP1, C1R, SVEP1, VCAN and SPTB) but not yet characterized in muscle tissue. To this end, we analyzed their expression (1) during muscle aging in WT mice (5 and 24 months), (2) in SOD1G93A-transfected myotube cells in vitro, (3) in a muscle-specific SOD1G93A mouse model (5 and 24 months), and (4) in a systemic SOD1G93A transgenic mouse at different disease stages (60 and 120 days) by quantitative PCR. All eight target genes were expressed in skeletal muscle and most of them showed increased transcription with aging. In ALS models, gene expression was significantly overexpressed at early stages, particularly in muscle-specific (MLC/SOD1G93A) and systemic (SOD1G93A) models, mimicking aging-related profiles. These alterations attenuated with disease progression, suggesting an early transient muscle response to ALS-linked SOD1 mutations. Hence, this study demonstrates that sarcopenia-associated proteins are actively expressed and modulated in skeletal muscle during aging and ALS and suggests convergent response mechanisms.
SN - 1422-0067
ER -