Abstract
Healthy aging and longevity are a growing topic of interest. They depend on the complex interplay between nuclear and mitochondrial DNA, the environment and the microbiota, that is, the whole set of bacteria living in the different parts of our body with their whole set of genes. Understanding this complex nature versus nurture balance is one of the greatest challenges in human genetics and human health. What is the influence of genomic and epigenomic variants as well as immune system over aging? How much does our microbiome interfere in or contribute to our health or our diseases? Could our microbiome help explaining the missing heritability in complex disorders? This proposal aims to address these questions through different approaches and expertise. Data on cognitive maintenance, brain structure and function (MRI) will be obtained. Socio-demographic measures in various depths will contribute to establish the panorama of environmental contributions and their influence on health and longevity. Functional models, particularly at the cellular level, will be an essential part of the array of techniques we plan to deploy in order to understand specific mechanisms behind normal and pathological aging processes. In an attempt to enhance our comprehension on these questions we will investigate three large samples of individuals: a) healthy individuals from São Paulo older than 60 who have been followed for many years and will be the study sample of most of the proposed projects in our portfolio (SABE cohort); b) a collection of data from individuals over 50 years of age who died of natural causes, from the Brazilian brain bank; c) a sample of individuals with genetic disorders associated with accelerated deterioration or complex disorders that could be partly caused by the human microbiome. Individuals enrolled in the São Paulo population-based samples have a highly admixed background and might have a different structure from the populations of other Brazilian regions. Therefore, in order to validate our molecular findings in other Brazilian populations, we also plan to incorporate populations from different regions and ethnic and environmental backgrounds: Aquilombo population, which is mainly African-derived and a cohort from Paraíba, which is highly inbred. Additionally, it will be included one sample of nonagenarians’ individuals and other of overweight adults with a high proportion of European (Italians, Germans, Pomeranians, Austrians and Portuguese) and Afro-Amerindian ancestry from Vitória (ES). Patients and animal models with focus on early aging diseases, and neuromuscular and neurodegenerative disorders will be investigated. Our main goal is to elucidate factors playing major roles in the wide range of variation observed in aging, also taking advantage of pathological genetic phenotypes, to enhance our understanding on normal longevity. In order to achieve this goal, the establishment of the present network, with researchers from different States, is fundamental. It will allow us to assemble a large collection of individuals of different ethnicities, which lack for the Brazilian population, and which is essential for the population-based studies here proposed. It is also important to point out that the group from S. Paulo has already a long-standing collaboration with the researchers from other States which has already resulted in several publications. Another aim of this proposal is the Education project, disseminating Science, which aims to stimulate the curiosity and to motivate the public for topics related to Genetics. Posters with provocative questions on Genetics will be distributed on subway stations, bus terminals and in public schools, referring to a hot site that can be accessed by mobile phone. The first campaign, "Similar, but different", is underway in São Paulo (http://www.qenoma.ib.usp.br). The research partners of other states will coordinate these campaigns in their own regions. In order to achieve all these goals we have assembled a group of expertise in different areas of interest, such as molecular biology (at the nuclear and mitochondrial DNA, RNA or protein level), others with experience on imaging, as well as immunology, metagenomics and bioinformatics and computational science. (AU)
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