Abstract
Recent studies revealed a key role of mitochondria in the 'axis of aging'. Mitochondrial dysfunction induces ROS production, leading to genotoxic damage, increasing erosion of telomeres followed by the activation of p53, blocking the mitochondrial biogenesis and generating a vicious cycle which induces the age-related mitochondrial dysfunction. This study, based on proteomic analysis, aims to elucidate the role of different mitochondrial subpopulations in the aging of heart in a rat model. Subsarcolemmal (SS) mitochondria play a major role in the adaptation of cells to physiological stimuli, whereas intermyofibrillar (IMF) mitochondria, are “power plants” for cardiac muscle contraction. The two subpopulations were isolated according to their localization in young (6 months), old adult (22 months) and senescent (30 months) Sprague Dawley rats by differential centrifugation in a density gradient. The differences at proteomic level were monitored by 2D-DIGE coupled with Maldi Tof and ESI MS/MS. While only few significant differences were detected in whole cardiac muscle proteome among young, adult and old rats, we detected many differences in SS mitochondrial proteome, particularly related to cell metabolism, cytoskeletal organization, membrane permeability and chaperon proteins indicating that aging may affect the SS mitochondria to maintain heart tissue homeostasis. Proteome of IMF mitocondria was characterized by a different pattern as compared to SS mitochondria and the number of proteins changed in aging were lower, even though a progression was observed from 22 to 30 months. These preliminary results suggest that protein dysregulation in mitochondrial proteome could significantly contribute to age-dependent impairment of cardiac function. However, these changes are not appreciable when analyzing the heart muscle proteome as a whole, highlighting the relevance of sub-cellular fractionation to detect molecular events involved in the aging process.
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