Striking Age-associated Iron Increase
in [Nutrition]
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From: ironjustice on 7 Aug 2008 11:45 Iron accumulation with age, oxidative stress and functional decline. Xu J, Knutson MD, Carter CS, Leeuwenburgh C Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't] PLoS ONE 2008; 3(8):e2865. 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. PLoS ONE [PLoS ONE] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
From: ironjustice on 7 Aug 2008 11:59 On Aug 7, 8:45 am, ironjustice <ironjust...(a)cashette.com> wrote: Iron accumulation with age << "Iron might contribute to muscle atrophy" Increased iron content and RNA oxidative damage in skeletal muscle with aging and disuse atrophy. Hofer T, Marzetti E, Xu J, Seo AY, Gulec S, Knutson MD, Leeuwenburgh C, Dupont-Versteegden EE Exp Gerontol 2008 Feb 29. Muscle atrophy with aging or disuse is associated with deregulated iron homeostasis and increased oxidative stress likely inflicting damage to nucleic acids. Therefore, we investigated RNA and DNA oxidation, and iron homeostasis in gastrocnemius muscles. Disuse atrophy was induced in 6- and 32-month old male Fischer 344/ Brown Norway rats by 14 days of hind limb suspension (HS). We show that RNA, but not DNA, oxidative damage increased 85% with age and 36% with HS in aged muscle. Additionally, non-heme iron levels increased 233% with aging and 83% with HS at old age, while staining for free iron was strongest in the smallest fibers. Simultaneously, the mRNA abundance of transferrin receptor-1 decreased by 80% with age and 48% with HS for young animals, while that of the hepcidin regulator hemojuvelin decreased 37% with age, but increased about 44% with disuse, indicating a dysregulation of iron homeostasis favoring increased intracellular free iron in atrophied muscles. RNA and DNA concentrations increased with age and were negatively correlated with muscle mass, whereas protein concentrations decreased with aging, indicating a preferential loss of protein compared to nucleic acids. Furthermore, xanthine oxidase activity increased with age, but not with HS, while mRNA abundance of the Y box-binding protein-1, which has been suggested to bind oxidized RNA, did not change with age or HS. These results suggest that RNA oxidation, possibly mediated by increased non-heme iron, might contribute to muscle atrophy due to disuse particularly in aged muscle. Experimental gerontology [Exp Gerontol] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > Iron accumulation with age, oxidative stress and functional decline. > Xu J, Knutson MD, Carter CS, Leeuwenburgh C > Research Support, N.I.H., Extramural, Research Support, Non-U.S. > Gov't] > PLoS ONE 2008; 3(8):e2865. > > 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. > > PLoS ONE [PLoS ONE] > > -------------------------------------------------------------------------------- > > Who loves ya. > Tom > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > Man Is A Herbivore!http://tinyurl.com/4rq595 > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
From: jay on 7 Aug 2008 21:16
> > 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. > > These results suggest that RNA oxidation, possibly mediated by > increased non-heme iron, might contribute to muscle atrophy due to > disuse particularly in aged muscle. While Persistent Organic Pollutants (POPs) have been declining, most importantly in dietary fats, due to TCDD's long half life (10 yrs), it's levels is still increasing, although more slowly, in most persons. TCDD causes cells to increase production or iron-utilizing detox enzymes. Because the detox enzymes aren't able to neutralize TCDD, the can bind with GOD knows what else and in worst cases, create toxic intermediates that increase free radicals and DNA damage. |