, Volume 34, Issue 1, pp 95–109 | Cite as

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

  • Ehab H. Sarsour
  • Maneesh G. Kumar
  • Amanda L. Kalen
  • Monali Goswami
  • Garry R. Buettner
  • Prabhat C. Goswami


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.


Chronological lifespan Ageing Manganese superoxide dismutase Quiescence Hydroxytyrosol Mitochondria 



Adenoviruses carrying a dominant-negative form of human MnSOD cDNA


Chronological lifespan


Copper–zinc superoxide dismutase


Extracellular superoxide dismutase


Electron paramagnetic resonance


Glutathione peroxidase




Manganese superoxide dismutase


Multiplicity of infection


Normal human fibroblasts


Propidium iodide


Reactive oxygen species



We thank The University of Iowa EPR and Flow Cytometry Cores for assisting with EPR spectroscopy and flow cytometry assays. Funding from NIH CA 111365 and McCord Research foundation supported this work.

Supplementary material

11357_2011_9223_MOESM1_ESM.pdf (300 kb)
ESM 1 (PDF 300 kb)


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Copyright information

© American Aging Association 2011

Authors and Affiliations

  • Ehab H. Sarsour
    • 1
  • Maneesh G. Kumar
    • 1
  • Amanda L. Kalen
    • 1
  • Monali Goswami
    • 1
  • Garry R. Buettner
    • 1
  • Prabhat C. Goswami
    • 1
  1. 1.Free Radical and Radiation Biology Division, Department of Radiation OncologyThe University of IowaIowa CityUSA

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