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Aging-related changes in oxidative stress response of human endothelial cells

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Abstract

Background

Oxidative stress is strongly associated with aging and age-related diseases and plays a crucial role in endothelial dysfunction development.

Aim

To better understand the molecular mechanisms of aging and stress response in humans, we examined changes to young and older human endothelial cells over time (72, 96 and 120 h), before and after H2O2-induced stress.

Methods

We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation. Moreover, we quantified levels of cellular senescence by senescence-associated β galactosidase (SA-βgal) assay.

Results

Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels. In addition cellular senescence drastically increased in older cells compared with Young cells both in presence and in the absence of oxidative stress.

Discussion

By following the cell behavior during the time course, we can hypothesize that while in young cells an oxidative stress induction stimulated an adequate response through activation of molecular factor crucial to counteract oxidative stress, the older cells are not able to adequately adapt themselves to external stress stimuli.

Conclusions

During their life, endothelial cells impair the ability to defend themselves from oxidative stress stimuli. This dysfunction involves the pathway of Sirt1 a critical regulator of oxidative stress response and cellular lifespan, underlining its crucial role in endothelial homeostasis control during aging and age-associated diseases.

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Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Human and Animal Rights

The article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Department of Medicine and Surgery, University of Salerno, Salerno, Italy

    Valeria Conti, Giusy Russomanno, Valentina Manzo & Amelia Filippelli

  2. Department of Medicine and Health Sciences, University of Molise, Via Giovanni Paolo II - Località Tappino, 86100, Campobasso, Italy

    Graziamaria Corbi

  3. Laboratory of Pre-clinical and Translational Research, Reference Cancer Center of Basilicata, Scientific Institute of Hospitalization and Treatment, Rionero in Vulture, Pz, Italy

    Vittorio Simeon

  4. Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy

    Nicola Ferrara

  5. Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme, Benevento, Italy

    Nicola Ferrara

Authors
  1. Valeria Conti
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  2. Graziamaria Corbi
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  3. Vittorio Simeon
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  4. Giusy Russomanno
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  5. Valentina Manzo
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  6. Nicola Ferrara
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  7. Amelia Filippelli
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Corresponding author

Correspondence to Graziamaria Corbi.

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Conti, V., Corbi, G., Simeon, V. et al. Aging-related changes in oxidative stress response of human endothelial cells. Aging Clin Exp Res 27, 547–553 (2015). https://doi.org/10.1007/s40520-015-0357-9

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  • DOI: https://doi.org/10.1007/s40520-015-0357-9

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