Assessment of the Interaction Between Thymic Involution, Immunosenescence, and Metabolic Dysfunction in an Animal Model of Lipodystrophy

• Grant number: 23/16423-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2024
• End date: June 01, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Letícia de Souza Figueiredo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process, AP.TEM

Abstract

The challenge posed by aging is escalating with the global increase in life expectancy. As the elderly population expands, the incidence of chronic non-communicable and infectious diseases also rises, imposing a burden on public health systems. Aging is characterized by a progressive reduction in the body's functions, spanning from molecular aspects to entire systems, including the immune system. In this context, cellular senescence assumes a pivotal role, marked by the interruption of the cell cycle and the generation of inflammatory signals, culminating in the phenomenon known as "inflammaging." Within the immune system, this results in immunosenescence, encompassing thymic involution and the depletion of immune cells. The thymus, responsible for T cell maturation, undergoes atrophy, compromising the body's capacity to respond to novel challenges and diminishing the efficacy of the adaptive immune response. Conversely, metabolic dysfunction expedites the aging process. This project aims to investigate how metabolic dysfunction associated with lipodystrophy can accelerate immune system aging and, consequently, the overall aging of the body. Utilizing a lipodystrophic mouse model featuring the deletion of the Dicer enzyme in adipocytes, we will assess the impact of lipodystrophy on immunosenescence. Given that Dicer plays a crucial role in the miRNA biogenesis pathway, we will also examine the role of these molecules produced in adipocytes on the immune system. Our hypothesis posits that metabolic alterations triggered by the loss of adipocytes' ability to produce miRNAs contribute to thymic involution and early immunosenescence associated with lipodystrophy, rendering the organism more susceptible to disease development and mortality. Our study holds the potential to unveil novel mechanisms linked to the immunosenescence process and accelerated aging in the context of lipodystrophy, providing targets for senotherapeutic interventions that can enhance the quality of life for the elderly population and those grappling with metabolic dysfunction.