Multiple long-term conditions and immunosenescence: cellular senescence and clinical outcomes in sepsis.

• Grant number: 24/01637-7
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2025
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alessandra Gambero
• Grantee: Alessandra Gambero
• Host Institution: Escola de Ciências da Vida (ECV). Pontifícia Universidade Católica de Campinas (PUC-CAMP). Campinas , SP, Brazil
• Associated researchers: Elisa Donalisio Teixeira Mendes ; Saullo Haniell Galvão de Oliveira
• Associated scholarship(s): 25/02074-9 - Neutrophil senescence, comorbidities and clinical outcomes in sepsis, BP.DD

Abstract

Cellular senescence is a process that involves cell cycle arrest, the expression of b-galactosidase and a senescence-associated secretory phenotype (SASP) that alters the tissue microenvironment and compromises its functioning. Cellular senescence also affects the immune system, a process known as immunosenescence resulting from chronological aging (replicative senescence) or induced early by stressful events such as those triggered by metabolic changes, drugs, or persistent infections. Immunosenescence alters innate and adaptive responses by modifying the functioning of different immune cells through different mechanisms. With the aging of the population and the increasingly frequent occurrence of morbidities that can accelerate the emergence of immunosenescence, it is important to understand how morbidities determine immunosenescent processes and how immunosenescence alters clinical outcomes. Sepsis is still a public health challenge, the main cause of deaths within intensive care units (ICUs). According to the World Health Organization, sepsis kills 11 million people each year and disables millions more. In Brazil, it is estimated that 240,000 deaths occur each year as a result of sepsis. Our objective in this project is to collect data on the morbidity profile, whether absent, single, or multiple, of patients who were diagnosed with sepsis/septic shock at the Hospital da PUC-Campinas in the last 8 years. We also intend to evolve with knowledge about the role of multimorbidities in immunosenescence markers and whether patients with multimorbidities who present with sepsis present markers of neutrophilic immunosenescence that are associated with clinical outcomes. In this way, we intend to contribute to the advancement of knowledge on the subject that may in the future lead to new therapies that target cellular senescence (senotherapeutics) or other approaches that can modify outcomes in patients with multimorbidities and sepsis. (AU)