Iron Accumulation During Cellular Senescence in Human Fibroblasts In Vitro
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Iron accumulates as a function of age in several tissues in vivo and is associated with the pathology of numerous age-related diseases. The molecular basis of this change may be due to a loss of iron homeostasis at the cellular level. Therefore, changes in iron content in primary human fibroblast cells (IMR-90) were studied in vitro as a model of cellular senescence. Total iron content increased exponentially during cellular senescence, resulting in 10-fold higher levels of iron compared with young cells. Low-dose hydrogen peroxide (H2O2) induced early senescence in IMR-90s and concomitantly accelerated iron accumulation. Furthermore, senescence-related and H2O2-stimulated iron accumulation was attenuated by N-tert-butylhydroxylamine (NtBHA), a mitochondrial antioxidant that delays senescence in vitro. However, SV40-transformed, immortalized IMR-90s showed no time-dependent changes in metal content in culture or when treated with H2O2 and/or NtBHA. These data indicate that iron accumulation occurs during normal cellular senescence in vitro. This accumulation of iron may contribute to the increased oxidative stress and cellular dysfunction seen in senescent cells.
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Iron accumulation occurs in replicative senescent fibroblasts in vitro.
“Iron accumulation occurs in replicative senescent fibroblasts in vitro [35] and the iron storage protein ferritin is enriched in ageing tissues [36], [37].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [35]
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BackgroundPrevention of mutation, Cancer, and other Age-Associated diseases by optimizing micronutrient intake
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- Authors
- Killilea, D. W., Atamna, H., Liao, C., & Ames, B. N.
- Affiliations
- University of California, Berkeley (US)
- Children's Hospital Oakland Research Institute, Oakland, CA 94609
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2003-10
- Volume
- 5
- Issue
- 5
- Pages
- 507-516
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- PMC
- PMC4503765
- OpenAlex
- W2004604872
- Cited by
- 92
- References
- 50
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 6 · 2023: 12 · 2022: 10 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2013: 1 · 2012: 2
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Medical Foundation
- National Institute on Aging (5 T32 AG00266-02, T32AG000266)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, iron accumulation, iron homeostasis, human fibroblasts, IMR-90 cells, hydrogen peroxide, oxidative stress, mitochondrial antioxidants, SV40-transformed cells, age-related diseases
- MeSH terms
- Cell Division, Cell Line, Cell Line, Transformed, Dose-Response Relationship, Drug, Fibroblasts, Humans, Hydrogen Peroxide, Hydroxylamines, Iron, Magnesium, Manganese, Potassium, Proteins, Spectrometry, X-Ray Emission, Time Factors, Umbilical Veins, Zinc, Cellular Senescence, Endothelial Cells, Cell Size
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