Intracellular free iron content is highly correlated with muscle fiber size after disuse in aged rats

X.J. Wang, C. Leeuwenburgh, E.E. Dupont-Versteegden
College of Medicine, University of Kentucky

Oxidative stress is a common phenomenon associated with age- and disuse-induced muscle atrophy and we showed previously that intracellular free iron is likely involved. The objective of this study was to investigate the role of free iron content in determination of muscle fiber size with disuse in gastrocnemius (GAS) muscles of young and old rats. Muscle atrophy was induced in 6- and 32-month old male Fisher 344/Brown Norway rats by 14 days of hind limb suspension (HS). Free iron content was measured histologically, enabling the direct comparison between fiber size and free iron content at the level individual muscle fibers.

The results showed that GAS weight and muscle fiber cross sectional area (CSA) were significantly smaller in 32-month old animals, when compared to 6-month old animals. In addition, HS was associated with a decrease in muscle weight and CSA of GAS in both young and old animals. Free iron concentration showed a significant negative correlation with muscle mass at the whole muscle level for all rats combined, as we showed previously. More interestingly, individual muscle fiber CSA was highly negatively correlated with free iron content in GAS muscles from old and to lesser extent from young rats. These data suggest that oxidative stress induced by high free iron content likely plays an important role in disuse-induced loss of muscle mass particularly in muscles from aged rats, and therefore interventions aimed to curtail accumulation of intracellular free iron may be useful in the elderly to prevent acute atrophy in response to inactivity.

Keywords: Muscle atrophy, Oxidative stress, Aging, Disuse, Iron