Publicação
Hormetic induction of antioxidant defenses for promotion of healthy aging
| Resumo: | 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. |
|---|---|
| Autores principais: | Carvalho, Ana Cristina Pontes |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866876485698060288 |
|---|---|
| author | Carvalho, Ana Cristina Pontes |
| author_facet | Carvalho, Ana Cristina Pontes |
| author_role | author |
| contributor_name_str_mv | Gomes, Andreia Lima, Cristóvão Fernando Macedo Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Carvalho, Ana Cristina Pontes\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Gomes, Andreia Lima, Cristóvão Fernando Macedo Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Carvalho, Ana Cristina Pontes |
| datacite.date.Accepted.fl_str_mv | 2017-12-20T00:00:00Z |
| datacite.date.available.fl_str_mv | 2020-12-20T07:00:15Z |
| datacite.date.embargoed.fl_str_mv | 2020-12-20T07:00:15Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.titles.title.fl_str_mv | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| dc.contributor.none.fl_str_mv | Gomes, Andreia Lima, Cristóvão Fernando Macedo Universidade do Minho |
| dc.creator.none.fl_str_mv | Carvalho, Ana Cristina Pontes |
| dc.date.Accepted.fl_str_mv | 2017-12-20T00:00:00Z |
| dc.date.available.fl_str_mv | 2020-12-20T07:00:15Z |
| dc.date.embargoed.fl_str_mv | 2020-12-20T07:00:15Z |
| dc.description.none.fl_str_mv | As pessoas vivem mais tempo mas muitas vezes sofrem de múltiplas doenças associadas ao envelhecimento, o que tem importantes implicações sociais e económicas. O consumo de frutas e vegetais tem sido associado a um risco reduzido de doenças relacionadas com o envelhecimento, mas a base científica para a estratégia de melhorar a saúde através da dieta ainda não está devidamente fundamentada. O objetivo principal desta tese de doutoramento foi esclarecer se a indução hormética de respostas celulares de stress por fitoquímicos, em particular através da via de sinalização Nrf2/ARE, tem efeitos antienvelhecimento e, nesse sentido, poderá explicar os efeitos benéficos para a saúde do consumo de frutas e vegetais. No capítulo 2, a extensa literatura disponível sobre curcumina foi revista. O uso ancestral de turmérico na medicina tradicional e a extensa investigação nas últimas décadas indicam que a curcumina é um candidato interessante para estratégias que visam alcançar um envelhecimento saudável. Atualmente estão a ser conduzidos estudos para superar as limitações do uso de curcumina em intervenções no envelhecimento. No capítulo 3, avaliou-se a capacidade dos diterpenos fenólicos ácido carnósico (CA) e carnosol (CS) de induzir defesas antioxidantes em fibroblastos humanos normais, o que foi relacionado com efeitos anti-envelhecimento. Ambos os compostos induziram defesas antioxidantes associadas à ativação da sinalização Nrf2. A resposta ao stress provocada pelo CS conferiu uma ação citoprotetora contra um estímulo tóxico posterior induzido pelo terc-butil hidroperóxido (t-BOOH), confirmando o seu efeito hormético. O CS protegeu igualmente contra a senescência prematura induzida por H2O2 e melhorou várias características das células em senescência replicativa in vitro. No capítulo 4, avaliou-se a capacidade de extratos de células de Hypericum perforatum (HP) e de células de Hypericum perforatum elicitadas com Agrobacterium tumefaciens (HP+AT) em proteger contra o stress oxidativo induzido em células HepG2. O extrato HP+AT inibiu significativamente a morte celular, a depleção de GSH e os danos no DNA induzida pelo t-BOOH, nos regimes de pré- e co-incubação. O extrato HP+AT induziu defesas antioxidantes associadas à ativação da sinalização Nrf2. Em conjunto, estes dados sustentam a visão de que os fitoquímicos podem ser considerados um meio para promover um envelhecimento saudável. Em particular, a indução hormética de respostas de stress pelo CS sustentam a importância de estudos posteriores que visem a sua utilização em intervenções no envelhecimento. |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/54204 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.title.fl_str_mv | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_db06 |
| description | 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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| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
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| identifier.url.fl_str_mv | https://hdl.handle.net/1822/54204 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
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| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/54204 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Carvalho, Ana Cristina Pontes |
| publishDate | 2017 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engengPeople 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.porAs pessoas vivem mais tempo mas muitas vezes sofrem de múltiplas doenças associadas ao envelhecimento, o que tem importantes implicações sociais e económicas. O consumo de frutas e vegetais tem sido associado a um risco reduzido de doenças relacionadas com o envelhecimento, mas a base científica para a estratégia de melhorar a saúde através da dieta ainda não está devidamente fundamentada. O objetivo principal desta tese de doutoramento foi esclarecer se a indução hormética de respostas celulares de stress por fitoquímicos, em particular através da via de sinalização Nrf2/ARE, tem efeitos antienvelhecimento e, nesse sentido, poderá explicar os efeitos benéficos para a saúde do consumo de frutas e vegetais. No capítulo 2, a extensa literatura disponível sobre curcumina foi revista. O uso ancestral de turmérico na medicina tradicional e a extensa investigação nas últimas décadas indicam que a curcumina é um candidato interessante para estratégias que visam alcançar um envelhecimento saudável. Atualmente estão a ser conduzidos estudos para superar as limitações do uso de curcumina em intervenções no envelhecimento. No capítulo 3, avaliou-se a capacidade dos diterpenos fenólicos ácido carnósico (CA) e carnosol (CS) de induzir defesas antioxidantes em fibroblastos humanos normais, o que foi relacionado com efeitos anti-envelhecimento. Ambos os compostos induziram defesas antioxidantes associadas à ativação da sinalização Nrf2. A resposta ao stress provocada pelo CS conferiu uma ação citoprotetora contra um estímulo tóxico posterior induzido pelo terc-butil hidroperóxido (t-BOOH), confirmando o seu efeito hormético. O CS protegeu igualmente contra a senescência prematura induzida por H2O2 e melhorou várias características das células em senescência replicativa in vitro. No capítulo 4, avaliou-se a capacidade de extratos de células de Hypericum perforatum (HP) e de células de Hypericum perforatum elicitadas com Agrobacterium tumefaciens (HP+AT) em proteger contra o stress oxidativo induzido em células HepG2. O extrato HP+AT inibiu significativamente a morte celular, a depleção de GSH e os danos no DNA induzida pelo t-BOOH, nos regimes de pré- e co-incubação. O extrato HP+AT induziu defesas antioxidantes associadas à ativação da sinalização Nrf2. Em conjunto, estes dados sustentam a visão de que os fitoquímicos podem ser considerados um meio para promover um envelhecimento saudável. Em particular, a indução hormética de respostas de stress pelo CS sustentam a importância de estudos posteriores que visem a sua utilização em intervenções no envelhecimento.application/pdfporHormetic induction of antioxidant defenses for promotion of healthy agingCarvalho, Ana Cristina PontesGomes, AndreiaLima, Cristóvão Fernando MacedoHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptURNurn:tid:1015053372020-12-20T07:00:15Z2017-12-2020172017-12-20T00:00:00ZHandlehttps://hdl.handle.net/1822/54204http://purl.org/coar/access_right/c_abf2open access5051117 bytesliteraturehttp://purl.org/coar/resource_type/c_db06doctoral thesishttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/e3cea4c1-d8ef-4359-8f99-2110cf1b3f79/download |
| spellingShingle | Hormetic induction of antioxidant defenses for promotion of healthy aging Carvalho, Ana Cristina Pontes |
| status | SINGLETON |
| title | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| title_full | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| title_fullStr | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| title_full_unstemmed | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| title_short | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| title_sort | Hormetic induction of antioxidant defenses for promotion of healthy aging |
| url | https://hdl.handle.net/1822/54204 |
| visible | 1 |