Cited by 69Iron Metabolism and DisordersNutrition and Health in AgingMuscle Physiology and Disorders

Aging-related changes in the iron status of skeletal muscle

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DeRuisseau, Keith C., Park, Young-Min, DeRuisseau, Lara R., Cowley, Patrick M., Fazen, Christopher H., Doyle, Robert P.·2013·Experimental Gerontology

Abstract

The rise in non-heme iron (NHI) concentration observed in skeletal muscle of aging rodents is thought to contribute to the development of sarcopenia. The source of the NHI has not been identified, nor have the physiological ramifications of elevated iron status in aged muscle been directly examined. Therefore, we assessed plantaris NHI and heme iron (HI) levels in addition to expression of proteins involved in iron uptake (transferrin receptor-1; TfR1), storage (ferritin), export (ferroportin; FPN), and regulation (iron regulatory protein-1 (IRP1) and -2 (IRP2)) of male F344xBN F1 rats (n=10/group) of various ages (8, 18, 28, 32, and 36 months) to further understand iron regulation in aging muscle. In a separate experiment, iron chelator (pyridoxal isonicotinoyl hydrazone; PIH) or vehicle was administered to male F344xBN F1 rats (n=8/group) beginning at 30 months of age to assess the impact on plantaris muscle mass and function at ~36 months of age. Principle findings revealed the increased NHI concentration in old age was consistent with concentrating effects of muscle atrophy and reduction in HI levels, with no change in the total iron content of the muscle. The greatest increase in muscle iron content occurred during the period of animal growth and was associated with downregulation of TfR1 and IRP2 expression. Ferritin upregulation did not occur until senescence and the protein remained undetectable during the period of muscle iron content elevation. Lastly, administration of PIH did not significantly (p>0.05) impact NHI or measures of muscle atrophy or contractile function. In summary, this study confirms that the elevated NHI concentration in old age is largely due to the loss in muscle mass. The increased muscle iron content during aging does not appear to associate with cytosolic ferritin storage, but the functional consequences of elevated iron status in old age remains to be determined.

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Crossref · 10.1016/j.exger.2013.08.011

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Authors
DeRuisseau, K. C., Park, Y.-M., DeRuisseau, L. R., Cowley, P. M., Fazen, C. H., & Doyle, R. P.
Affiliations
  • Syracuse University (US)
  • Le Moyne College (US)
Corresponding author
DeRuisseau, Keith C.
Venue
Experimental Gerontology
Publisher
Elsevier BV
Published
2013-11
Volume
48
Issue
11
Pages
1294-1302
ISSN
0531-5565 (ISSN-L)
OpenAlex
W2051266381
Cited by
69
References
50
Citations by year
2026: 3 · 2025: 11 · 2024: 14 · 2023: 8 · 2022: 10 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 1
FWCI
1.67
Type
journal article
Language
en
Open access
Locations
  • Experimental Gerontology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging of the National Institutes of Health (R03AG032033)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
skeletal muscle aging, non-heme iron, heme iron, sarcopenia, muscle atrophy, iron regulation, transferrin receptor 1, IRP2, ferritin, ferroportin, pyridoxal isonicotinoyl hydrazone, iron chelation, plantaris muscle, muscle mass, muscle contractility
MeSH terms
Ferroportin, Aging, Animals, Ferritins, Heme, Iron, Iron Chelating Agents, Isoniazid, Male, Muscle Contraction, Muscular Atrophy, Pyridoxal, Rats, Inbred BN, Rats, Inbred F344, Receptors, Transferrin, RNA, Messenger, Gene Expression, Muscle, Skeletal, Cation Transport Proteins, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Rats, Sarcopenia

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