Usando Biologia de Sistemas para entender a Imunossenescência

Detalhes bibliográficos
Autor(a) principal: Passos, Fernando Marcon
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
Texto Completo: https://teses.usp.br/teses/disponiveis/95/95131/tde-20230725-114626/
Resumo: não disponível
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spelling Usando Biologia de Sistemas para entender a Imunossenescêncianot availableEnvelhecimentoSistema imunenão disponívelThe immune system remodelling occurring with ageing, known as immunosenescence, contributes to increased susceptibility of the elderly to infectious diseases, cancer, autoimmunity, and decreased responses to vaccines. This remodelling is a poorly understood complex process that involves multiple factors. For instance, we still don’t known about the molecular mechanisms involved in immunosenescence and how they can be caused by primary problems, such as early perturbations in biological processes or secondary problems, such as those caused by a failed response to achieve homeostasis, disturbed by primary problems. Here we applied a Systems Biology framework to study the remodelling of the immune system by analysis of blood transcriptional profiles. We aim to understand how changes in the expression of immune components during life are related to immunosenescence. To this end, we developed novel methods tailored to identify and describe pathways and genes serving as biomarker of ageing. We applied these methods to a massive dataset from 1807 blood samples from healthy subjects gathered from public gene expression repositories. We found 56 transcripts correlated with age, which suggests that signal transduction pathways and cytokines in regulating T lymphocytes, especially regulatory, are important to cell proliferation and senescence. Coexpression modules related to innate and adaptive immune system signalling were identified. Changes in global expression patterns in these modules reveal imbalances in signal transduction mechanisms regulating the interaction between the innate and adaptive immune system, probably due to the deregulation of TLR activation pathways and the production of cytokines induced by NF-kB. We identified changes in these expression profiles around the age of 30 years and around the age of 55-60 years. These results suggest that transcriptional changes, that are characteristic of immunosenescence, occur at a young age and intensify with ageing. 3 The methodologies developed in this study allowed us to find transcriptional disorders matching morphological changes described in the literature and enabled us to identify new transcripts and biological processes not yet associated to immunosenescence. Such methodologies can be optimized and adapted not only to higher-quality transcriptomics assessment techniques, such as RNA-Seq, but also to other levels of biological information, such as metabolomics, proteomics, etc. We expect that our findings may assist in the comprehension of mechanisms involved in immunosenescence, and to aid in the creation of interventions capable of beneficial regulation of remodelling of the immune system during life, allowing the extension of a life with quality.Biblioteca Digitais de Teses e Dissertações da USPHelder Takashi Imoto NakayaPassos, Fernando Marcon2018-12-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://teses.usp.br/teses/disponiveis/95/95131/tde-20230725-114626/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesspor2023-07-27T13:43:05Zoai:teses.usp.br:tde-20230725-114626Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212023-07-27T13:43:05Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Usando Biologia de Sistemas para entender a Imunossenescência
not available
title Usando Biologia de Sistemas para entender a Imunossenescência
spellingShingle Usando Biologia de Sistemas para entender a Imunossenescência
Passos, Fernando Marcon
Envelhecimento
Sistema imune
title_short Usando Biologia de Sistemas para entender a Imunossenescência
title_full Usando Biologia de Sistemas para entender a Imunossenescência
title_fullStr Usando Biologia de Sistemas para entender a Imunossenescência
title_full_unstemmed Usando Biologia de Sistemas para entender a Imunossenescência
title_sort Usando Biologia de Sistemas para entender a Imunossenescência
author Passos, Fernando Marcon
author_facet Passos, Fernando Marcon
author_role author
dc.contributor.none.fl_str_mv Helder Takashi Imoto Nakaya
dc.contributor.author.fl_str_mv Passos, Fernando Marcon
dc.subject.por.fl_str_mv Envelhecimento
Sistema imune
topic Envelhecimento
Sistema imune
description não disponível
publishDate 2018
dc.date.none.fl_str_mv 2018-12-13
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://teses.usp.br/teses/disponiveis/95/95131/tde-20230725-114626/
url https://teses.usp.br/teses/disponiveis/95/95131/tde-20230725-114626/
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv
dc.rights.driver.fl_str_mv Liberar o conteúdo para acesso público.
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Liberar o conteúdo para acesso público.
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.coverage.none.fl_str_mv
dc.publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
publisher.none.fl_str_mv Biblioteca Digitais de Teses e Dissertações da USP
dc.source.none.fl_str_mv
reponame:Biblioteca Digital de Teses e Dissertações da USP
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Biblioteca Digital de Teses e Dissertações da USP
collection Biblioteca Digital de Teses e Dissertações da USP
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)
repository.mail.fl_str_mv virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br
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