Publication
Hormetic induction of antioxidant defenses for promotion of healthy aging
| Summary: | People are living longer but often suffer from multiple diseases related to aging which has important social and economic implications. Consumption of fruits and vegetables has been associated with reduced risk of age-related diseases but the scientific basis supporting the strategy to improve health through diet is largely missing. The main objective of this doctoral thesis was to clarify if the hormetic induction of cellular stress responses by phytochemicals, in particular the Nrf2/ARE signaling pathway, can provide anti-aging effects and therefore explain the health beneficial effects of consumption of fruits and vegetables. In chapter 2, the extensive available literature on curcumin was reviewed. The ancestral use of turmeric in traditional medicine and the extensive research over the last decades indicate that curcumin is an interesting candidate for interventions to achieve healthy aging. Currently, investigations are being conducted to overcome the limitations of the use of curcumin in aging interventions. In chapter 3, the ability of the phenolic diterpenes carnosic acid (CA) and carnosol (CS) to induce antioxidant defenses in normal human fibroblasts was evaluated and related with anti-aging effects. CA and CS induced antioxidant defenses in human fibroblasts associated with Nrf2 signaling. The stress response elicited by CS conferred a cytoprotective action against a following oxidant challenge with tert-butyl hydroperoxide (t-BOOH), confirming its hormetic effect. CS also protected against H2O2-induced premature senescence and ameliorated several features in cells undergoing replicative senescence in vitro. In chapter 4, the ability of extracts of Hypericum perforatum cells (control HP) and of Hypericum perforatum cells elicited with Agrobacterium tumefaciens (elicited HP) to protect against oxidative stress induced in HepG2 cells was evaluated. The methanolic extract of elicited HP, in contrast to the one from control HP, significantly inhibited t- BOOH-induced cell death, GSH depletion and DNA damage, in pre- and co- incubation regimes. The elicited HP extract significantly induced antioxidant defenses, whereas the extract of control HP did not, and that induction was associated with Nrf2 signaling. Overall, these findings support that phytochemicals can be viewed as a mean to promote healthy aging. In particular, the hormetic induction of stress responses by CS in normal human cells supports its further development for nutraceutical interventions during aging. |
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| Main Authors: | Carvalho, Ana Cristina Pontes |
| Year: | 2017 |
| Country: | Portugal |
| Document type: | doctoral thesis |
| Access type: | open access |
| Associated institution: | Universidade do Minho |
| Language: | English |
| Origin: | RepositóriUM - Universidade do Minho |
| Summary: | People are living longer but often suffer from multiple diseases related to aging which has important social and economic implications. Consumption of fruits and vegetables has been associated with reduced risk of age-related diseases but the scientific basis supporting the strategy to improve health through diet is largely missing. The main objective of this doctoral thesis was to clarify if the hormetic induction of cellular stress responses by phytochemicals, in particular the Nrf2/ARE signaling pathway, can provide anti-aging effects and therefore explain the health beneficial effects of consumption of fruits and vegetables. In chapter 2, the extensive available literature on curcumin was reviewed. The ancestral use of turmeric in traditional medicine and the extensive research over the last decades indicate that curcumin is an interesting candidate for interventions to achieve healthy aging. Currently, investigations are being conducted to overcome the limitations of the use of curcumin in aging interventions. In chapter 3, the ability of the phenolic diterpenes carnosic acid (CA) and carnosol (CS) to induce antioxidant defenses in normal human fibroblasts was evaluated and related with anti-aging effects. CA and CS induced antioxidant defenses in human fibroblasts associated with Nrf2 signaling. The stress response elicited by CS conferred a cytoprotective action against a following oxidant challenge with tert-butyl hydroperoxide (t-BOOH), confirming its hormetic effect. CS also protected against H2O2-induced premature senescence and ameliorated several features in cells undergoing replicative senescence in vitro. In chapter 4, the ability of extracts of Hypericum perforatum cells (control HP) and of Hypericum perforatum cells elicited with Agrobacterium tumefaciens (elicited HP) to protect against oxidative stress induced in HepG2 cells was evaluated. The methanolic extract of elicited HP, in contrast to the one from control HP, significantly inhibited t- BOOH-induced cell death, GSH depletion and DNA damage, in pre- and co- incubation regimes. The elicited HP extract significantly induced antioxidant defenses, whereas the extract of control HP did not, and that induction was associated with Nrf2 signaling. Overall, these findings support that phytochemicals can be viewed as a mean to promote healthy aging. In particular, the hormetic induction of stress responses by CS in normal human cells supports its further development for nutraceutical interventions during aging. |
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