0000000000594500
AUTHOR
Arlette Gratas-delamarche
Growth hormone replacement therapy prevents sarcopenia by a dual mechanism: improvement of protein balance and of antioxidant defenses.
The aim of our study was to elucidate the role of growth hormone (GH) replacement therapy in three of the main mechanisms involved in sarcopenia: alterations in mitochondrial biogenesis, increase in oxidative stress, and alterations in protein balance. We used young and old Wistar rats that received either placebo or low doses of GH to reach normal insulin-like growth factor-1 values observed in the young group. We found an increase in lean body mass and plasma and hepatic insulin-like growth factor-1 levels in the old animals treated with GH. We also found a lowering of age-associated oxidative damage and an induction of antioxidant enzymes in the skeletal muscle of the treated animals. GH…
Inhibition of Xanthine Oxidase by Allopurinol Prevents Skeletal Muscle Atrophy: Role of p38 MAPKinase and E3 Ubiquitin Ligases
International audience; Abstract Top Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS) are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in ratsand its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinaseand the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, …
Allopurinol partially prevents disuse muscle atrophy in mice and humans
AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The pro…
Inactivity-induced oxidative stress: A central role in age-related sarcopenia?
Ageing causes a progressive decline in skeletal muscle mass that may lead to decreased strength and functionality. The term sarcopenia is especially used to characterise this geriatric syndrome. Numerous conditions and behaviours are considered to accelerate the progression of sarcopenia such as chronic diseases, malnutrition and physical inactivity. As people in modern countries are more and more sedentary, the impact of physical inactivity on the prevalence of sarcopenia might be more and more important in the future. In this review, we discuss how reactive oxygen species (ROS) could mediate the effects of lifelong inactivity in the onset and progression of age-related sarcopenia. Althoug…