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Immunosenescence and energetic sensors: potential influence of visceral adipose tissue and aerobic fitness

Grant number: 19/10187-7
Support type:Scholarships abroad - Research
Effective date (Start): January 02, 2020
Effective date (End): June 30, 2020
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Fábio Santos de Lira
Grantee:Fábio Santos de Lira
Host: Ana Maria Miranda Botelho Teixeira
Home Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
Local de pesquisa : Universidade de Coimbra (UC), Portugal  

Abstract

The level of cardiorespiratory fitness is considered a potential modifier of the inverse association between visceral obesity and mortality. Combined with this factor, low-grade inflammation promotes insulin resistance and adiponectin as well as dysregulation of the adaptive immune system such as T lymphocytes. The energy demand of T lymphocytes is regulated by nutrient sensors such as mTORC, in which it contributes positively to cell growth and proliferation and regulates the function of regulatory T lymphocytes. Therefore, the objective of this study is to investigate adult and elderly men the impact of mTORC1 and mTORC 2 pathways on the regulation of Treg and Th17 lymphocytes, and inflammatory responses according to levels of cardiorespiratory fitness and visceral adiposity in adult and elderly males. An initial screening will be performed to measure and classify individuals' body composition and nutritional habits. Participants will be recruited between the ages of 18 and 35 and equal or greater than 60 years. A maximum incremental test will be performed to determine the aerobic and anaerobic threshold, aerobic capacity. Fasting blood samples will be collected for the evaluation of the inflammatory profile, insulin and cortisol. In cell culture, T lymphocytes will be treated with IL-2 plus TGF-² to differentiate into Treg or IL-6 plus TGF-² to differentiate into Th17. After differentiation, Treg and Th17 will be treated with either rapamycin or leucine (inhibitor of mTORC1 and stimulator, respectively) and torin 1 or PIP3 (inhibitor of mTORC2 and stimulator, respectively). Inflammatory markers will be determined in the culture medium. The data will be handled appropriately using SPSS version 24 and GraphPad Prism v.7.0. In all analyzes, significance will be set at p <0.05.