Research Description:

The Role of Mitochondrial Bioenergetics in Sarcopenia

One popular theory explaining senescence implicates free radicals, specifically, reactive oxygen species (ROS) such as superoxide anion (O2 ● -), hydroxyl radicals (OH-), and peroxide (H2O2) as the cause.  It is widely accepted that electron leaks and inefficiencies in the electron transport chain (ETC) mechanism lead to cumulative ROS production and tissue damage.  Accumulated ROS mediated damage to mitochondria can increase mitochondrial dysfunction and lead to decreased ATP production, amplified ROS production due to damaged respiratory complexes, and potentially apoptosis.  In this study, we investigate the effect of 40% caloric restriction intervention on aging and the respiratory chain enzymes in skeletal muscle mitochondria.

This study will be conducted in 4 different groups of rats: two sets of middle-age groups (18 months), one fed an Ad Libitum (AD) diet and the other on a 40% caloric restricted (CR) diet.  The two old groups (37 months) were also divided in a similar manner.  Upon sacrifice skeletal muscle will be isolated and the mitochondria will be extracted by differential centrifugation.  Mitochondrial respiratory function will be determined by high-resolution oxygraphy.  The specific materials used in the highly sensitive oxygraph limit non-mitochondrial O2 consumption background.  We will determine oxygen consumption at resting (without ADP, state IV) and active state (with ADP, state III).  The respiratory control ratio (RCR) calculation will allow us to quantify the efficiency of oxidation and phosphorylation in mitochondria.  Additionally, ETC complex content, activity, and oxidative damage will be assessed via blue native polyacrylamide gel electrophoresis (BN-PAGE) separation of the different complexes.

The mitochondrial respiratory chain is both a source and a target of ROS and plays a central regulatory role in apoptosis.  Accrued ROS mediated damage may play a key role sarcopenia, the degenerative age-related loss of muscle mass and strength.  This study will further our understanding of mitochondrial dysfunction and its role in sarcopenia.