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Investigating autophagic mechanisms in mice with accelerated senescence

Grant number: 22/00482-4
Support Opportunities:Regular Research Grants
Duration: November 01, 2022 - October 31, 2024
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Joilson de Oliveira Martins
Grantee:Joilson de Oliveira Martins
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Anderson de Sá Nunes ; Stephen Fernandes de Paula Rodrigues


Aging is a natural and multifactorial process characterized by a gradual loss of physiological integrity, impaired normal and essential functions to survival of the body, and leading to the development of age-related diseases. In this context, autophagy, a process of intracellular content degradation, is regulated naturally by the mammalian target nutrient receptor of rapamycin (mTOR) or chemically by the drug rapamycin (RAPA) and chloroquine (CQ), has a direct relationship with cellular homeostasis and maintenance of the senescent phenotype. In order to better understand how changes in glucose metabolism caused by autophagic mechanisms, potentiated by RAPA or reduced by CQ, regulate the senescent phenotype of lymphocytes and impact metabolically active tissues and organs, this project seeks to investigate the relationship between glucose metabolism and autophagy, in the regulation of the senescent lymphocyte phenotype, employing Senescence-Accelerated Mouse Prone 8 (SAM-P8) and Senescence-Accelerated Mouse Resistant 1 (SAM-R1). For this purpose, the following parameters will be evaluated: (1) molecular and cellular mechanisms associated with senescence such as: changes in the blood metabolic and hematimetric profile, changes in genetic markers, in the cytokine profile, the presence of apoptosis in histologic structure, in bone marrow, spleen, thymus, muscle, pancreas, and liver samples, and alterations of lymphocytes population (blood, spleen and thymus) and neutrophils (blood); (2) the relationship between autophagy modulation and the senescence phenotype, through the signaling of proteins involved in the activation of autophagy; (3) changes in glucose sensitivity and metabolism, such as: changes in glucose metabolism in vivo and in vitro, respiratory capacity, number of mitochondria, membrane potential, and production of ROS in lymphocytes and hepatocytes cultivated in vitro. (AU)

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