title: Iron accumulation with age, oxidative stress and functional decline.
abstract: Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted 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 approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects.
authors.affiliation: Department of Aging and Geriatrics, Division of Biology of Aging, Genomics and Biomarkers Core of The Institute on Aging, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Jinze
authors.initials: J
authors.lastname: Xu
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Knutson
authors.forename: Christy S
authors.initials: CS
authors.lastname: Carter
authors.forename: Christiaan
authors.initials: C
authors.lastname: Leeuwenburgh
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D003433:Crosses, Genetic; D004247:DNA / Q000378:metabolism; D004038:Diet, Reducing; D002149:Energy Intake; D005260:Female; D018737:Hand Strength / Q000502:physiology; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012313:RNA / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344
chemical_list: D006454:Hemoglobins; D012313:RNA; D004247:DNA; D007501:Iron