Reversing age-associated immunosenescence in master athletes: cellular and molecular mechanisms of health

• Grant number: 19/25626-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2021
• Effective date (End): March 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Fábio Santos de Lira
• Grantee: Luciele Guerra Minuzzi
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil
• Associated scholarship(s): 22/02723-9 - Exercise-induced metabolic reprogramming of NK cells: the mTORC1 pathway or adrenergic signalling, BE.EP.PD

Abstract

Immunosenescence is the progressive dysfunction of the immune system that occurs with aging and results in greater susceptibility to infections, autoimmune diseases, and cancer. There is evidence that exercise is a safe intervention to reduce immunosenescence. The purpose of this study is to explore the effects of lifelong exercise on several markers of immunosenescence and inflammation while investigating the cellular, molecular, and metabolic mechanisms involved. Master athletes; physically active individuals stratified by age (over 40 and under 30 yrs) and two age-matched control groups, will be recruited. Initial screening will be performed to evaluate body composition and nutritional habits. VO2max will be determined by a maximal incremental protocol. Blood samples will be collected before (Pre) for biochemical markers, flow cytometry, and cell culture analysis, immediately after (Post), and 2 h after (2h) the test for flow cytometry, and homing and apoptosis assays. T lymphocytes and NK cells will be identified and quantified by flow cytometry. CD4+ T lymphocytes will be cultured and differentiated into Tregs in the presence or absence of IL-2 plus TGF-² and/or the presence or absence of IL-6 plus TGF-² to Th17-induced differentiation. The production of pro- and anti-inflammatory cytokines will be determined in these culture media. NK cells will be isolated and stimulated with IL-2 and IL-15, and the expression of different cell surface markers will be carried out using flow cytometry. Besides, apoptotic and homing markers will be analyzed by gene expression and quantification as well as CD56dim and CD56bright NK cell subsets expressing granzyme and perforin. Statistical analysis will be performed using GraphPad Prism v.8.0 software. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MINUZZI, LUCIELE GUERRA; LIRA, FABIO SANTOS; BONETTI DE POLI, RODRIGO ARAUJO; FIALHO LOPES, VITHOR HUGO; ZAGATTO, ALESSANDRO MOURA; SUZUKI, KATSUHIKO; ANTUNES, BARBARA M.. High-intensity intermittent exercise induces a potential anti-inflammatory response in healthy women across the menstrual cycle. CYTOKINE, v. 154, p. 7-pg., 2022-06-01. (19/25626-6)

DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; MINUZZI, LUCIELE GUERRA; LIRA, FABIO SANTOS; VIEIRA PEREIRA GONCALVES, ANA SOFIA; MARTINHO, ANTONIO; ROSA NETO, JOSE CESAR; TEIXEIRA, ANA MARIA. Improvement in the anti-inflammatory profile with lifelong physical exercise is related to clock genes expression in effector-memory CD4+T cells in master athletes.. EXERCISE IMMUNOLOGY REVIEW, v. 27, p. 17-pg., 2021-01-01. (19/10187-7, 19/09854-9, 16/01409-8, 18/24187-6, 15/16777-0, 18/19678-0, 19/25626-6)

ROSA-NETO, JOSE CESAR; LIRA, FABIO SANTOS; LITTLE, JONATHAN PETER; LANDELLS, GRAHAM; ISLAM, HASHIM; CHAZAUD, BENEDICTE; PYNE, DAVID B.; TEIXEIRA, ANA MARIA; BATATINHA, HELENA; ANTUNES, BARBARA MOURA; et al. Immunometabolism-fit: How exercise and training can modify T cell and macro- phage metabolism in health and disease. EXERCISE IMMUNOLOGY REVIEW, v. 28, p. 45-pg., 2022-01-01. (19/25626-6)

SILVA, BRUNA SPOLADOR DE ALENCAR; PEREIRA, TELMO; MINUZZI, LUCIELE GUERRA; PADILHA, CAMILA SOUZA; FIGUEIREDO, CAIQUE; OLEAN-OLIVEIRA, TIAGO; DOS SANTOS, IVETE VERA MEDEIROS; VON AH MORANO, ANA ELISA; MARCHIOTO, OSMAR; RIBEIRO, JOSE PROCOPIO JABUR; et al. Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit-COVID study. FRONTIERS IN IMMUNOLOGY, v. 14, p. 16-pg., 2023-09-11. (20/07765-6, 21/11932-8, 21/06338-0, 19/26378-6, 19/25626-6, 18/23402-0)

FREIRE, ANA PAULA COELHO FIGUEIRA; LIRA, FABIO SANTOS; MORANO, ANA ELISA VON AH; PEREIRA, TELMO; COELHO-E-SILVA, MANUEL-JOAO; CASEIRO, ARMANDO; CHRISTOFARO, DIEGO GIULLIANO DESTRO; MARCHIOTO JUNIOR, OSMAR; DORNELES, GILSON PIRES; MINUZZI, LUCIELE GUERRA; et al. ole of Body Mass and Physical Activity in Autonomic Function Modulation on Post-COVID-19 Condition: An Observational Subanalysis of Fit-COVID Stud. NTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALT, v. 19, n. 4, FEB 2022. (19/25626-6)