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Cellular and molecular mechanisms involved in cardiac aging: effects of cardiomyocyte-specific suppression of NF-kB

Grant number: 19/06435-5
Support type:Regular Research Grants
Duration: October 01, 2019 - September 30, 2021
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Ana Paula Cremasco Takano
Grantee:Ana Paula Cremasco Takano
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Aging population is rapidly growing. Longevity is an achievement, but it is accompanied by an unfavorable question, as aging is related to the development of many diseases. In this context, cardiovascular diseases are the leading cause of morbidity and mortality in elderly people. Aging causes damage to the structure and function of the heart, resulting from cellular and tissue processes involving inflammation and oxidative stress. The NF-kB transcription factor is responsible for mediating responses that occur in such conditions and, consequently, represents a possible agent able to integrate cellular and molecular mechanisms that occur in cardiac tissue. The mechanisms include cellular senescence, telomere length alteration associated with increased susceptibility to DNA damage, dysregulation of cell signaling, among others. The main objective is to evaluate the participation of NF-kB in the mechanisms driving the aging heart. To address this question, transgenic mice with cardiac-specific suppression of NF-kB will be used and submitted to natural and/ or D-galactose-induced aging. We will evaluate: a) functional parameters; b) morphological aspects; c) cellular senescence; and d) other aging-associated mechanisms, such as DNA damage, cardiomyocyte apoptosis, autophagy markers, antioxidant enzymes, signaling pathways associated with longevity such as IGF-1R, mTOR, AMPK and SIRT1. The results will contribute to better understand the mechanisms involved in the cardiac aging process. This knowledge may lead to the development of new therapeutic strategies in order to benefit individuals who gradually age and may have the postponement or attenuation of cardiac manifestations associated with cardiovascular diseases. (AU)