Thesis, COLLÉGIALITÉ, FRANZEN Rachelle

Abstract

Sarcopenia is a geriatic syndrome characterized by an age-related progressive loss of muscle mass and strength, which carries multiple personal, economic and social burdens. With the ever so growing improvements in the healthcare system and in the lifestyle conditions, its incidence is expected to rise in the upcoming years. Although the etiologic context of this syndrome is vastly heterogeneous, recent studies have highlighted the role of mitochondria and mitochondrial dysfunction in its onset. Skeletal muscle—a high metabolically active tissue that is especially vulnerable to mitochondrial dysregulations. Slight alterations in the mitochondrial function can lead to significant clinical manifestations. This study was conducted within the framework of a Wallonia Region financed collaborative R&D project called MitoSir, which brings together multiple research partners— including ULiege (CORD), RevaTis SA., GenFlow Bioscience and ULB— to explore potential of stem cells as a therapeutic strategy to sarcopenia . In this study, we used an immortalized human myoblast cell line (LHCN-M2) and an exogenous hydrogen peroxide (H2O2 ) treatment on adherent LHCN-M2 cells to simulate an oxidative environment potentially inductive of a mitochondrial dysfunction, two hallmarks of sarcopenia. Our High-Resolution Respirometry (HRR) results showed that the exogenous H2O2 treatment increases mitochondrial leak respiration in a time- and dose-dependent manner. ETSmax showed a tendency to decrease. Finally, results from the CellTiter-Glo assay, used to evaluate cellular ATP content, corroborate these findings, showing a dose-dependent collapse in ATP levels following H2O2 treatment without inducing cell mortality. Globally speaking, our results point towards a mitochondrial dysfunction that might derive from multiple oxidative actions of H2O2 within the cell.