Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity

Vittorio Calabrese, Carolin Cornelius, Albena T. Dinkova-Kostova, Ivo Iavicoli, Rosanna Di Paola, Aleardo Koverech, Salvatore Cuzzocrea, Enrico Rizzarelli, Edward J. Calabrese

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    255 Citations (Scopus)

    Abstract

    Modulation of endogenous cellular defense mechanisms represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. This paper introduces the emerging role of exogenous molecules in hormetic-based neuroprotection and the mitochondrial redox signaling concept of hormesis and its applications to the field of neuroprotection and longevity. Maintenance of optimal long-term health conditions is accomplished by a complex network of longevity assurance processes that are controlled by vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, such as polyphenols and L-carnitine/acetyl-L-carnitine, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways: including vitagenes. Hormesis provides the central underpinning of neuroprotective responses, providing a framework for explaining the common quantitative features of their dose response relationships, their mechanistic foundations, their relationship to the concept of biological plasticity as well as providing a key insight for improving the accuracy of the therapeutic dose of pharmaceutical agents within the highly heterogeneous human population. This paper describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways including sirtuin, Nrfs and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. (C) 2011 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)753-783
    Number of pages31
    JournalBiochimica et Biophysica Acta. Molecular Basis of Disease
    Volume1822
    Issue number5
    DOIs
    Publication statusPublished - May 2012

    Cite this

    Calabrese, V., Cornelius, C., Dinkova-Kostova, A. T., Iavicoli, I., Di Paola, R., Koverech, A., Cuzzocrea, S., Rizzarelli, E., & Calabrese, E. J. (2012). Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochimica et Biophysica Acta. Molecular Basis of Disease, 1822(5), 753-783. https://doi.org/10.1016/j.bbadis.2011.11.002