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AGING AND OBESITY: MITOCHONDRIA AT THE HEART OF THE PROBLEM

Abstract

David E. Lee, Richard A. Perry, Jr., Jacob L. Brown, Lemuel A. Brown, Megan E. Rosa, Tyrone A. Washington, & Nicholas P. Greene. University of Arkansas, Fayetteville, Arkansas; e-mail: Davidlee@uark.edu

The mitochondrial theory of aging implicates reactive oxygen species (ROS) produced during oxidative metabolism in damaging cardiac muscle cells and contributing to the physiological decline of aging. Mitochondrial DNA (mtDNA) is damaged by ROS and cannot be accurately transcribed or translated into proteins needed for oxidative metabolism leading to detriments in oxidative capacity of cardiac muscle with age. Obesity is also strongly associated with multiple cardiomyopathies and mitochondrial damage and my exacerbate effects of aging. If mitochondrial mRNA translation plays a role in the onset of cardiomyopathy is unclear. PURPOSE: The purpose of this investigation was to describe mitochondrial content (COX-IV), biogenesis (PGC-1α, TFAM), mitochondrial mRNA translation machinery (12S and 16S rRNAs, mtIF2/3, TUFM, TACO1) and the mitochondrially encoded protein (CytB) during aging and obesity. METHODS: Four groups of C57BL/6J mice were used: Young Lean (3-4 weeks old, normal diet, n=10, YL), Young diet-induced obese (n=16, YO), Aged Lean (20-24 months old, n=8, AL), and Aged Obese (n=6, AO). Hearts were removed, weighed, snap-frozen, and processed for protein and RNA for immunoblotting and real time RT-PCR, respectively. RESULTS: COX-IV protein was ~30% greater in aged mice compared to young (ppp<0.05) while TFAM protein was unchanged among groups (p>0.05). 12S was ~50% lower in aged compared to young (p<0.05) and ~30% lower in obese compared to lean (p<0.05). 16S content was ~30% lower in AL and AO vs. YL and ~70% lower in YO vs. YL (p<0.05). mtIF2 protein was ~40% less in aged vs. young (p<0.05). Obese mice showed ~25% less TACO1 protein compared to Lean (p<0.05). CytB protein was ~40% lower in aged vs. young (p<0.05). CONCLUSION: This investigation has taken clear steps showing alterations in mitochondrial content and mRNA translation machinery in aged hearts, concomitant with decreases in the content of mitochondrial encoded protein. These impairments in mitochondrial mRNA translation are indicative of greater oxidative stress in cardiac tissue during aging, which may directly impact the development of cardiomyopathies such as ventricular hypertrophy and cardiac fibrosis.

Funding provided by the Arkansas Bioscience Institute

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