The Influence Of Age And Lifelong Sedentary Behavior On Mitochondrial Function In Skeletal Muscle

Abstract

One of the most adversely age-affected tissues is skeletal muscle. Indeed, aging is associated with a loss of skeletal muscle mass (i.e., sarcopenia) and a progressive decline in the fiber's ability to maintain homeostasis, in part, due to mitochondrial dysfunction. However, it is unclear whether these age-related changes in muscle mass and mitochondrial function are due to aging per se, or due to prolonged sedentary behavior. PURPOSE: This study investigated the impact of lifelong inactivity on both skeletal muscle mass and skeletal muscle mitochondrial function. METHODS: Young (3 months), mature (18 months) and old (25 months) male C57BL/6 mice were studied from two experimental groups: 1) Sedentary (housed in standard cage); and 2) Active (housed in cage with running wheel). At the completion of the experiment, muscle weights were obtained, tests of mitochondrial function were performed, and biomarkers of oxidative damage to mitochondrial proteins were determined. RESULTS: Our findings indicate that aging is associated with a diminished respiratory function of skeletal muscle mitochondria. Additionally, lifelong inactivity exacerbates sarcopenia and the age-related decline in skeletal muscle mitochondrial respiratory function. Moreover, our data reveal that the age- and sedentary-related decline in mitochondrial function is associated with higher levels of mitochondrial oxidative damage. CONCLUSIONS: Collectively, these data indicate that beyond aging per se, lifelong inactivity is a major determinant in the etiology of both sarcopenia and skeletal muscle mitochondrial dysfunction. This work was supported by a grant- Fundação para a Ciência e Tecnologia (PTDC/10DES/70757/2006).