Iron and AtrophyHofer T, Marzetti E, Xu J, Seo AY, Gulec S, Knutson MD, Leeuwenburgh
C, Dupont-Versteegden EE
Increased iron content and RNA oxidative damage in skeletal muscle
with aging and disuse atrophy. [JOURNAL ARTICLE]
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]
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