Immunosenescence on Chronic Obstructive Pulmonary Disease

• Grant number: 18/06063-8
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2018 - August 31, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Gil Benard
• Grantee: Gil Benard
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Celso Ricardo Fernandes de Carvalho ; Cibele Cristine Berto Marques da Silva
• Associated scholarship(s): 20/00775-6 - Telomerase activity determined by real time PCR in COPD patients, and healthy smokers and non-smokers individuals, BP.TT

Abstract

Immunosenescence in chronic obstructive pulmonary disease patientsChronic obstructive pulmonary disease (COPD) é a disease characterized by obstruction of airflow, with non-specific and variables clinical features. The worldwilde COPD prevalence has increased due to increased exposure to risk factors as cigarette smoke, biomass exposure, and higher atmospheric pollution. This major exposure aggregated to higher life expectancy made COPD epidemic. Most of the patients present the disease after 40 years old, suggesting a strict relation of COPD pathogenesis with aging. Many aging characteristic are also present in COPD as telomeric damage, cellular senescence epigenetic modifications, lost of protein homeostasis and modifications in cellular and intracellular communication. The aim of the project is to verify whether accelerated senescence phenotype is due to cigarette smoke or the pathological injuries of COPD, or both. To this purpose mononuclear cells and serum from three groups of individuals, patients with COPD, smokers without pulmonary alteration (according to pulmonary function tests), and healthy elder will be used to analyze senescence markers. First, mononuclear cells telomerase enzyme will be quantified by PCR and ELISA and the mononuclear cells will be split into purified CD4 and CD8 lymphocyte subpopulations to evaluate telomere length by flow cytometry. In the sera of the threel groups we will measure oxidative stress products: H2O2, malondialdehyde, nitric oxide as well as total antioxidant capacity. To expand previous findings of our research group we will evaluate T cell subpopulations by flow cytometry uingh the following markers: CCR7, CD45RA, CD28, CD27, CD57, CD62L, CD127, CD69, CD25, FOXP3, and IL-17 production by ELISPOT. We hope to determine mechanisms underlying the accelerated senescence, either related to pathological changes that take place in COPD, or related to mechanisms triggered by cigarette smoke. The identification of the altered mechanisms for senescence can pave the way to new therapeutic targets aiming at improving COPD patients' quality of life and better prognosis. (AU)

Scientific publications

(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)

FERNANDES, JULIANA RUIZ; CARVALHO PINTO, THALYTA NERY; ARRUDA, LIA BARBARA; BERTO MARQUES DA SILVA, CIBELE CRISTINE; FERNANDES DE CARVALHO, CELSO RICARDO; CARVALHO PINTO, REGINA MARIA; DA SILVA DUARTE, ALBERTO JOSE; BENARD, GIL. ge-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adult. IMMUNITY & AGEING, v. 19, n. 1, FEB 14 2022. (18/06063-8)

FERNANDES, JULIANA RUIZ; PINTO, THALYTA NERY CARVALHO; PIEMONTE, LUCAS LOPES; ARRUDA, LIA BARBARA; DA SILVA, CIBELE CRISTINE BERTO MARQUES; CARVALHO, CELSO R. F.; PINTO, REGINA MARIA CARVALHO; DUARTE, ALBERTO J. S.; BENARD, GIL. Long-term tobacco exposure and immunosenescence: Paradoxical effects on T-cells telomere length and telomerase activity. MECHANISMS OF AGEING AND DEVELOPMENT, v. 197, JUL 2021. (18/06063-8)

THALYTA NERY CARVALHO PINTO; JULIANA RUIZ FERNANDES; LIÃ BARBARA ARRUDA; ALBERTO JOSÉ DA SILVA DUARTE; GIL BENARD. Cost-Effective Trap qPCR Approach to Evaluate Telomerase Activity: an Important Tool for Aging, Cancer, and Chronic Disease Research. Clinics, v. 76, 2021-02-05. (18/06063-8)