Calorie restriction attenuates age‐related iron accumulation and oxidative stress in skeletal muscle and improves indices of sarcopenia

It is well accepted that iron accumulates with senescence(definition) in several organs, but little is known about iron accumulation in muscle. We investigated the non‐heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted (CR) diet (60% of ad libitum food intake starting at 4 months of age) at 8, 18, 29 and 37 months of age. Total non‐heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non‐heme iron concentration increased by 200% in AL‐fed rats. Muscle iron concentrations correlated positively with the levels of oxidized RNA and negatively with the muscle mass and grip strength. The striking age‐associated increases in non‐heme iron and decreases in sarcopenia indices were all attenuated in the CR rats. Moreover, the age‐associated decrease of two key hematological parameters, Hct and Hb, in the AL rats was ameliorated by CR, whereas liver non‐heme iron concentration did not change over time in CR rats. These findings strongly suggest that the age‐related accumulation in muscle iron contributes to increased oxidative stress and sarcopenia, and that caloric restriction(definition) effectively attenuates these negative effects. This research was supported by grants AG17994, AG21042, DK065064, 1 P30 AG028740.