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Iron accumulation with age, oxidative stress and functional decline.

Xu J, Knutson MD, Carter CS, Leeuwenburgh C - PLoS ONE (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

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Effect of aging and calorie restriction on grip strength.Grip strength in CR rats declined significantly at 37 months of age, while it decreased significantly at 29 months of age in AL rats, yet more pronounced in advanced age of 37 months. Values are means±SEM (n = 7–8). a,b,cDifferent letters indicate values are significantly different (p<0.05 by Tukey's Multiple Comparison Test).
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pone-0002865-g004: Effect of aging and calorie restriction on grip strength.Grip strength in CR rats declined significantly at 37 months of age, while it decreased significantly at 29 months of age in AL rats, yet more pronounced in advanced age of 37 months. Values are means±SEM (n = 7–8). a,b,cDifferent letters indicate values are significantly different (p<0.05 by Tukey's Multiple Comparison Test).

Mentions: Grip strength is an excellent indicator of muscle strength and it correlates significantly with sarcopenia and mortality [36], [37], [40]. In our study, there was a significant age-related decline for grip strength in the AL groups with a 13% decrease at 18 months (p>0.05), 26% decrease at 29 months (p<0.05) and 64% decrease at 37 months (p<0.001) as compared to 8-month-old rats, respectively (Fig. 4). The significant decrease of grip strength was already noticeable before 29 months of age in AL rats, whereas there was no significant decrease in grip strength in CR rats until 37 months of age. Most importantly, the CR rats at 37 months of age showed equivalent grip strength to 8-month-old AL rats. In general, the age-associated decline in grip strength was significantly attenuated by CR in all age groups (p<0.05), indicating that CR partly prevents the decline in physical performance with age (Fig. 4).


Iron accumulation with age, oxidative stress and functional decline.

Xu J, Knutson MD, Carter CS, Leeuwenburgh C - PLoS ONE (2008)

Effect of aging and calorie restriction on grip strength.Grip strength in CR rats declined significantly at 37 months of age, while it decreased significantly at 29 months of age in AL rats, yet more pronounced in advanced age of 37 months. Values are means±SEM (n = 7–8). a,b,cDifferent letters indicate values are significantly different (p<0.05 by Tukey's Multiple Comparison Test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2481398&req=5

pone-0002865-g004: Effect of aging and calorie restriction on grip strength.Grip strength in CR rats declined significantly at 37 months of age, while it decreased significantly at 29 months of age in AL rats, yet more pronounced in advanced age of 37 months. Values are means±SEM (n = 7–8). a,b,cDifferent letters indicate values are significantly different (p<0.05 by Tukey's Multiple Comparison Test).
Mentions: Grip strength is an excellent indicator of muscle strength and it correlates significantly with sarcopenia and mortality [36], [37], [40]. In our study, there was a significant age-related decline for grip strength in the AL groups with a 13% decrease at 18 months (p>0.05), 26% decrease at 29 months (p<0.05) and 64% decrease at 37 months (p<0.001) as compared to 8-month-old rats, respectively (Fig. 4). The significant decrease of grip strength was already noticeable before 29 months of age in AL rats, whereas there was no significant decrease in grip strength in CR rats until 37 months of age. Most importantly, the CR rats at 37 months of age showed equivalent grip strength to 8-month-old AL rats. In general, the age-associated decline in grip strength was significantly attenuated by CR in all age groups (p<0.05), indicating that CR partly prevents the decline in physical performance with age (Fig. 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus