Journal article
MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan
Age, Vol.34(1), pp.95-109
02/2012
DOI: 10.1007/s11357-011-9223-7
PMCID: PMC3260369
PMID: 21384152
Abstract
Chronological lifespan (CLS) is defined as the duration of quiescence in which normal cells retain the capacity to reenter the proliferative cycle. This study investigates whether hydroxytyrosol (HT), a naturally occurring polyphenol found in olives, extends CLS in normal human fibroblasts (NHFs). Quiescent NHFs cultured for a long duration (30–60 days) lose their capacity to repopulate. Approximately 60% of these cells exit the cell cycle permanently; a significant increase in the doubling time of the cell population was observed. CLS was extended in quiescent NHFs that were cultured in the presence of HT for 30–60 days. HT-induced extension of CLS was associated with an approximately 3-fold increase in manganese superoxide dismutase (MnSOD) activity while there was no change in copper–zinc superoxide dismutase, catalase, or glutathione peroxidase protein levels. Quiescent NHFs overexpressing a dominant-negative mutant form of MnSOD failed to extend CLS. HT suppressed age-associated increase in mitochondrial ROS levels. Results from spectroscopy assays indicate that HT in the presence of peroxidases can undergo catechol–semiquinone–quinone redox cycling generating superoxide, which in a cellular context can activate the antioxidant system, e.g., MnSOD expression. These results demonstrate that HT extends CLS by increasing MnSOD activity and decreasing age-associated mitochondrial reactive oxygen species accumulation.
Details
- Title: Subtitle
- MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan
- Creators
- Ehab H Sarsour - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181 USAManeesh G Kumar - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181 USAAmanda L Kalen - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181 USAMonali Goswami - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181 USAGarry R Buettner - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181 USAPrabhat C Goswami - Free Radical and Radiation Biology Division, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181 USA
- Resource Type
- Journal article
- Publication Details
- Age, Vol.34(1), pp.95-109
- DOI
- 10.1007/s11357-011-9223-7
- PMID
- 21384152
- PMCID
- PMC3260369
- NLM abbreviation
- Age (Dordr)
- ISSN
- 0161-9152
- eISSN
- 1574-4647
- Publisher
- Springer Netherlands; Dordrecht
- Language
- English
- Date published
- 02/2012
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047631002771
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