Cited by 183Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsRedox biology and oxidative stress

Superoxide Dismutase 1 Knock-down Induces Senescence in Human Fibroblasts

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Blander, Gil, de Oliveira, Rita Machado, Conboy, Caitlin M., Haigis, Marcia, Guarente, Leonard·2003·Journal of Biological Chemistry

Abstract

Reactive oxygen species (ROS) such as superoxide radicals are responsible for the pathogenesis of various human diseases. ROS are generated during normal metabolic process in all of the oxygen-utilizing organisms. The copper-zinc-containing SOD (SOD1) acts as a major defense against ROS by detoxifying the superoxide anion. In model organisms, SOD1 has been shown to play a role in the aging process. However, the exact role of the SOD1 protein in the human aging process remains to be resolved. We show that SOD1 RNA interference (RNAi) induces senescence in normal human fibroblasts. This premature senescence depends on p53 induction. In contrast, in human fibroblastic cells with inactivated p53, the SOD1 RNAi is without effect. Surprisingly, in cancer cells (HeLa), the SOD1 RNAi induces cell death rather then senescence. Together, these findings support the notion that in normal human cells the SOD1 protein may play a role in the regulation of cellular lifespan by p53 and may also regulate the death signals in cancer cells.

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Crossref · 10.1074/jbc.m307146200

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Authors
Blander, G., de Oliveira, R. M., Conboy, C. M., Haigis, M., & Guarente, L.
Affiliations
Massachusetts Institute of Technology (US)
Corresponding author
Guarente, Leonard
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-10
Volume
278
Issue
40
Pages
38966-38969
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2129326379
Cited by
183
References
28
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 8
FWCI
4.79
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
superoxide dismutase 1, cellular senescence, premature senescence, p53 activation, human fibroblasts, reactive oxygen species, superoxide, aging, cellular lifespan, cancer cell death, HeLa cells, RNA interference
MeSH terms
Aging, Anions, beta-Galactosidase, Cell Line, Fibroblasts, Genetic Vectors, HeLa Cells, Humans, Microscopy, Fluorescence, Oxygen, Plasmids, Superoxide Dismutase, Transfection, Tumor Cells, Cultured, Blotting, Western, Tumor Suppressor Protein p53, Cellular Senescence, Cell Death, Reactive Oxygen Species, Transgenes, RNA Interference

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