Lifelong exercise as a pacemaker of T cell energetic metabolism and its impact on adaptive immune function in different life phases

• Grant number: 23/09216-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 15, 2024
• End date: October 03, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Fábio Santos de Lira
• Grantee: Bruna Spolador de Alencar Silva
• Supervisor: Manuel João Cerdeira Coelho e Silva
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Institution abroad: Universidade de Coimbra (UC), Portugal
• Associated to the scholarship: 21/11932-8 - Immunometabolism and SARS-CoV-2: The central role of fat body mass and physical fitness during the COVID-19 pandemic, BP.PD

Abstract

The major aim of this study is to explore the mechanisms involved in the metabolic programming of CD4+ T cells dependent on regular exercise as a potential determinant for better immune function. The questions that we propose to address in this proposal are:1) Does metabolic preferences of CD4+T cells change over time (from adolescence to old age) and explain their functionality changes? 2) Does regular exercise modulate CD4+T subtype function (naive, memory, EMRAs and senescent) by reprogramming energy metabolism? 3) Is CD4+T metabolic programming time dependent of regular exercise, favoring lifelong exercisers? Our hypothesis is that lifelong exercise might contribute to programming of T cell metabolism, preventing or attenuating the impairment observed in the overweight/obese and aging, favoring to the anti-inflammatory effects arising from regular practice of exercise. We suggest that a significant nutrient available to the CD4+ T cell could support oxidative metabolism, improve ATP production, thereafter favor quiescent state in these immune cells, as well as promote rapid activation function, when required. Therefore, lifelong exercisers would have a preserved immune response, indicating that they are better prepared to respond to new immune challenges, such as a SARS-CoV-2 infection. For this, we will recruit a group of male master athletes (endurance) (over 50 years old), a healthy age-matched control group (non-trained), a group of male young athletes (endurance) (up to 30 years old), a health young age-matched group (non-trained) of men, a group of male adolescents athletes (endurance) (14 to 18 years old- post peak height velocity (PHV)), and healthy adolescents age-matched control group of men. The participants will complete comprehensive health, diet, training habits screening-questionnaires and maximal incremental test (cycle ergometer). Evaluation of body composition (DXA), blood samples, and inflammatory status will be carried out. In order to assess if a predominance of more efficient metabolic pathways substantially impact CD4+ T cell functions of individuals trained throughout their lives, firstly we will assess CD4+ T cell metabolism at rest and after stimulation by cell culture (to produce cytokines or proliferation) in all groups. If our hypothesis of a programming of CD4+ T metabolism impact this cell function by exercise throughout life we will explore energy metabolism on the function of different CD4+ T cell subtypes (naive, memory, senescent). Also, we will investigate the effect of AMPK energy sensor in the process of CD4+ T differentiation into Tregs and Th17 cells in the different culture assays (activator (AICAR) and inhibitor (Dorsomorphin (compound C (CC)) of AMPK), an in vitro test with the aim of mimic the acute effect of an exercise session. (AU)