Mitochondrial remodeling underlying age-induced skeletal muscle wasting: let's talk about sex

Data de publicação: 01/01/2024

Autores da FMUP

Joaquim Adelino Correia Ferreira Leite Moreira

Autor

Participantes de fora da FMUP

Moreira-Pais A.
Vitorino R.
Sousa-Mendes C.
Neuparth M.J.
Nuccio A.
Luparello C.
Attanzio A.
Novák P.
Loginov D.
Nogueira-Ferreira R.
Oliveira P.A.
Ferreira R.
Duarte J.A.

Unidades de investigação

Cirurgia e Fisiologia
Laboratório Associado RISE- Rede de Investigação em Saúde

Investigador

Fernando Carlos De Landér Schmitt
RISE-Health

Investigador

Fernando Carlos De Landér Schmitt

Abstract

Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics. © 2024 The Authors

Dados da publicação

ISSN/ISSNe:: 0891-5849, 1873-4596
Tipo:: Article
Páginas:: 68-81
DOI:: 10.1016/j.freeradbiomed.2024.04.005
Link para outro recurso:: www.scopus.com

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Filiações

Moreira-Pais A.:: Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto (FADEUP) and Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, 4200-450, Portugal

LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, 3810-193, Portugal

Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Vila Real, 5000-801, Portugal
Vitorino R.:: iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, 3810-193, Portugal
Sousa-Mendes C.:: Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, 4200-319, Portugal
Neuparth M.J.:: Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto (FADEUP) and Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, 4200-450, Portugal

UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), Gandra, 4585-116, Portugal
Nuccio A.:: LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, 3810-193, Portugal

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, 90128, Italy
Luparello C.:: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, 90128, Italy
Attanzio A.:: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, 90128, Italy
Novák P.:: Laboratory of Structural Biology and Cell Signalling, Institute of Microbiology of the Czech Academy of Sciences, Prumyslova 595, Vestec, CZ-252 50, Czech Republic
Loginov D.:: Laboratory of Structural Biology and Cell Signalling, Institute of Microbiology of the Czech Academy of Sciences, Prumyslova 595, Vestec, CZ-252 50, Czech Republic
Nogueira-Ferreira R.:: Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, 4200-319, Portugal
Leite-Moreira A.:: Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, 4200-319, Portugal

Department of Cardiothoracic Surgery, Centro Hospitalar Universitário São João, Porto, 4200-319, Portugal
Oliveira P.A.:: Centre for Research and Technology of Agro Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, Vila Real, 5000-801, Portugal
Ferreira R.:: Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, 4200-319, Portugal
Duarte J.A.:: UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), Gandra, 4585-116, Portugal

Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, Gandra, 4585-116, Portugal

Keywords

Aging; Animals; Estradiol; Female; Fibrosis; Male; Mitochondria; Mitochondria, Muscle; Mitophagy; Muscle, Skeletal; Muscular Atrophy; Proteome; Rats; Sarcopenia; Sex Factors; Ubiquitin-Protein Ligases; androgen receptor; electron transferring flavoprotein; estradiol; estrogen receptor alpha; parkin; proteome; pyruvate dehydrogenase; pyruvate dehydrogenase E1; testosterone; unclassified drug; estradiol; parkin; proteome; ubiquitin protein ligase; adult; animal experiment; animal model; animal tissue; Article; bone age; bone remodeling; controlled study; enzymatic assay; fatty acid oxidation; female; immunoblotting; liquid chromatography-mass spectrometry; male; middle aged; mitochondrion; mitophagy; muscle atrophy; myofibrosis; nonhuman; protein fingerprinting; protein processing; rat; sex difference; signal transduction; testosterone blood level; Wistar rat; young adult; aging; animal; fibrosis; genetics; metabolism; mitochondrion; muscle atrophy; muscle mitochondrion; pathology; sarco