Aging Impairs Skeletal Muscle Mitochondrial Bioenergetic Function

Abstract

This study investigated the influence of age on the functional status of mitochondria isolated from skeletal muscle of C57BL/6 mice aged 3 and 18 months. We hypothesized that skeletal muscle mitochondria isolated from aged animals will exhibit a decreased respiratory function. Mitochondrial respiratory functional measures (ie, State 3 and 4 respiration, respiratory control ratio and number of nanomoles of ADP phosphorylated by nanomoles of O(2) consumed per mitochondrion) and biochemical markers of oxidative damage (aconitase activity, protein carbonyl derivatives, sulfhydryl groups, and malondialdehyde) were measured in isolated mitochondrial suspensions. Along with traditional tests of mitochondrial function, an in vitro repetitive ADP-stimulation test was used to evaluate the mitochondrial capacity to reestablish the homeostatic balance between successive ADP stimulations. The number of mitochondria per mitochondrial suspension, calculated by transmission electron microscopy, was used to normalize functional and biochemical data. Our results confirm the existence of an age-associated decline in mitochondrial function of mixed skeletal muscle, which is significantly correlated with higher levels of mitochondrial oxidative damage.

Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

“…A large body of evidence connects oxidative damage to mitochondrial DNA and proteins with aging changes, especially in keratinocytes and fibroblasts from photoaged skin [24]. Figueiredo and colleagues using a variety of parameters, validated the notion that aging affects the morphology and functional status of mitochondria [25].…”

Nrf2 deficiency promotes apoptosis and impairs PAX7/MyoD expression in aging skeletal muscle cells

“…Further, in Nrf2- null mice age-associated oxidative stress and apoptotic events are accompanied by increased ubiquitination of a wide range of proteins and lipid peroxidation (4-hydroxy nonenol, 4-HNE) (9). Increased ROS/RNS generation and prolonged oxidative/nitrosative stress contribute to damage and dysfunction of organelles and cells in several age-associated diseases in humans (4, 15, 31-36). However, it is currently unknown whether Nrf2 is required for proliferation and differentiation of myoblasts undergoing severe oxidative stress.…”

Effect of lifestyle on age-related mitochondrial protein oxidation in mice cardiac muscle

“…Although we observed an agerelated activity decline of respiratory chain complexes (Table 2), which is in agreement with previous studies (Choksi and Papaconstantinou 2008;Nair 2005), only succinate-ubiquinone reductase and cytochrome c reductase presented lifestyle-associated differences, with a significant decrease in activity in S mice ( Table 2). The notion that a sedentary behavior results in a general impairment of cardiac mitochondrial functionality was not as evident as in other tissues like skeletal muscle (Alves et al 2010;Figueiredo et al 2009), which might be explained by the permanent heart contractile activity.…”

“…Herein, we studied the effect of lifelong sedentary behavior on cardiac mitochondria functionality and susceptibility to oxidative damage. We select an animal model where mice have free access to running wheel once it better mimics the normal intermittent exercise routine of animals in the wilderness (Eisele et al 2008;Figueiredo et al 2009). Its effectiveness was confirmed by the cardiac hypertrophy observed in A mice, assessed through the heart/body weight ratio (Table 1), which is generally seen as a sign of cardiac adaptation to meet higher energy demands (Eisele et al 2008;Rosa et al 2005).…”