Role of mitochondria in the development of oxidative stress in skeletal muscle during aging

Abstract

During aging, a loss of muscle mass (sarcopenia) is observed. This phenomenon contributes to a decrease in the organism defence capa-cities, and lowers mobility and autonomy of elderly individuals. This work was undertaken to determine if oxidative stress could be implicated in sarcopenia, and in particular free radicals produced by mitochondria.

We showed that in glycolytic muscles, mitochondrial H₂O₂ production (MHP) derived from reverse electron flow between II and I complexes increased with age. In oxidative muscles, MHP derived from normal electron flow also increased. Thus, MHP increases with age in all muscle types, and the observed reduction of GPX activity in glycolytic muscles could aggravate the consequences of this phenomenon. However, other mitochondrial parameters remained unchanged with age (respiration, complex II to IV activities). In addition, calcium stress (induced by in vivo injection of the A23187 ionophore) had no effect in young rats, but induced muscle atrophy in the soleus, and an increase in MHP in the gastrocnemius of old rats.

These results suggest that MHP increase during healthy aging has no major effect on muscle aging on a short-term basis. It could have a significant effect in older ages, and/or contribute to a lower resistance of aged muscle to stress as observed with calcium.