Evaluation of the impact of autophagy on the regulation of senescent phenotype in lymphocyte of animal model treated with rapamycin

Abstract

Autophagy is an essential metabolic pathway for cellular homeostasis process, which Perform a constitutive and active function in controlling the biosynthesis of proteins and organelles, furthermore, it is a genetically regulated and conserved cellular process. This pathway is naturally regulated by the nutrient sensing receptor denominated the mechanistic target of Rapamycin (mTOR) or chemically by the drug rapamycin (RAPA), having a direct association with cell homeostasis and maintenance of the senescent phenotype. Senescence is an irreversible cellular state that contributes to the aging process, altering the metabolism and functions of the cell, 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 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. (AU)