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Regulation of the mTOR receptor by rapamycin in accelerated senescence mice: the role of autophagy in the aging process

Grant number: 22/05928-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 01, 2023
Effective date (End): April 30, 2024
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Joilson de Oliveira Martins
Grantee:Luiz Adriano Damasceno de Queiroz
Supervisor: Naima Moustaid-Moussa
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Texas Tech University (TTU), United States  
Associated to the scholarship:20/05439-4 - Regulation of mTOR receptor by rapamincin in senescence accelerated mice: the role of autophagy in aging process, BP.DR


Aging is a natural and multifactorial process characterized by a gradual loss of physiological integrity, impairing normal and essential functions to survival of the body, and leading to the development of age-related diseases, increasing the vulnerability to death of the organism. In this context, autophagy, a process of degradation of intracellular content, naturally regulated by the nutrient receptor sensor mammalian target of rapamycin (mTOR) or chemically by the drug rapamycin (RAPA), has a direct relationship with cell homeostasis and maintenance of the senescent phenotype. Senescence is a cellular state that contributes to the aging process, altering the cell's metabolism and functions, causing local and systemic damage over time, both at the level of tissues and organs, as well as at the level of the immune and endocrine systems. Wording better agreement how changes in glucose metabolism caused by the induction of autophagy, due to inhibition of mTOR by RAPA, regulate the senescent lymphocyte phenotype and impact on 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, in Senescence-Accelerated Mouse Prone 8 (SAM-P8) and Senescence-Accelerated-Resistant 1 Mouse (SAM-R1). For this purpose: (1) molecular and cellular mechanisms associated with senescence will be evaluated, such: changes in the blood metabolic profile by photometry, as well as changes in genetic markers by qPCR, in the cytokine profile by ELISA, and the presence of apoptosis in histologic structure by immunohistochemistry, in muscle, pancreas, spleen and liver samples, and alterations of lymphocytes population of blood and spleen by flow cytometry; (2) the relationship between autophagy modulation and the senescence phenotype, replacing evaluation of the signaling of proteins involved in the activation of autophagy by Western blot; (3) changes in glucose sensitivity and metabolism, such: changes in glucose metabolism in vivo by insulin tolerance test (ITT) and glucose (GTT), and in vitro by metabolomics, in respiratory capacity by seahorse, in the number of mitochondria by qPCR, in the production of ROS by flow cytometry in lymphocytes and hepatocytes cultivate in vitro. (AU)

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