Impact of Lifelong Sedentary Behavior on Mitochondrial Function of Mice Skeletal Muscle

Abstract

This study investigated the impact of lifelong sedentariness on skeletal muscle mass and mitochondrial function. Thirty C57BL/6 strain mice (2 months) were randomly divided into three groups (young-Y; old sedentary-OS; old active-OA). Young animals were sacrificed after 1 week of quarantine, and OS and OA groups were individually placed into standard cages and in cages with running wheels, respectively, until sacrifice (25 months). Body weights and hind-limb skeletal muscle wet weights were obtained from all groups. Mitochondrial respiratory functional measures (i.e., state 3 and 4 respiration, respiratory control ratio, and ratio of nanomoles of ADP phosphorylated by nanomoles of O2 consumed [ADP/O]) and biochemical markers of oxidative damage (aconitase activity, protein carbonyl derivatives, sulfhydryl groups) were measured in isolated mitochondrial suspensions. Our results reveal that lifelong sedentary behavior has a negative impact on the age-related loss of skeletal muscle mass and on the isolated mitochondrial function of mixed skeletal muscle of mice, which is associated with an increased oxidative damage to mitochondrial biomolecules.

Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle cross-sectional area

“…Furthermore, adult and old HSP10-overexpressing mice demonstrated reduced protein carbonyl content compared with adult wild-type mice (77 and 62% of adult wildtype, respectively). Several studies demonstrated increased content of protein carbonyls in mitochondria of muscles of old rodents (2,15), and this increase was enhanced by sedentary behavior (15). Our findings suggest that overexpression of HSP10 prevents the age-related accumulation of oxidized mitochondrial proteins observed in muscles of old wild-type mice.…”

“…The mitochondrial theory of aging proposed by Harman (19) was that oxidative damage to mitochondrial DNA, proteins, and lipid membranes accumulates over time due to ROS produced by the electron transport chain. Oxidative damage to mitochondrial proteins has been shown to increase with age in skeletal muscle (2,15). This damage to key components of the mitochondria is thought to result in aberrant ROS production by the electron transport chain, which in turn results in further damage, eventually resulting in mitochondria with impaired ATP production (3,25,41).…”

Alterations in intrinsic mitochondrial function with aging are fiber type‐specific and do not explain differential atrophy between muscles

“…Another point of interest revealed by our results is that a decline in muscle mitochondrial content with aging, which has been suggested in some reports (Chabi et al, 2008), but not others (Mathieu-Costello et al, 2005;Figueiredo et al, 2009), depends on the muscle examined and is generally not a feature of aging muscles. The fact that there is no decline in mitochondrial content in fast muscle, despite the documented decline in peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) in fast muscles like the Gas and plantaris (Chabi et al, 2008) with aging, implicates reduced mitochondrial protein turnover in producing the respiratory dysfunction (unchanged respiratory capacity per mg of muscle mass, despite higher oxphos protein levels) we have observed in the fast muscles, as suggested previously .…”

“…Firstly, we showed that one of the most widely studied manifestations of accumulated mtDNA damage on muscle mitochondrial phenotype, which being a selective deficiency in the activity of complex IV (cytochrome c oxidase; COX) in muscle fibers (Wanagat et al, 2001;Bua et al, 2006), occurs with very low frequency (< 0.2%) even in severely atrophied aging muscle, and COX deficient myofibers are not particularly atrophied compared to other myofibers in aged muscle (Rowan et al, 2011). In addition, we recently showed that mitochondrial isolation, which is one of the primary methods used to interrogate mitochondrial function in skeletal muscle, including many studies in aging muscle (Desai et al, 1996;Capel et al, 2005;Muller et al, 2007;Chabi et al, 2008;Seo et al, 2008;Figueiredo et al, 2009;Gouspillou et al, 2010), markedly alters the function of mitochondria compared to permeabilized myofibers, a preparation that preserves the mitochondrial structure and allows study of the whole mitochondrial population . Further to this point, mitochondrial isolation markedly exaggerated the severity of mitochondrial dysfunction in severely atrophied aging muscle (Picard et al, 2010).…”

Sedentary Behavior and Cancer: A Systematic Review of the Literature and Proposed Biological Mechanisms

“…For example, a recent trial found that 2 weeks of bed rest with eucaloric diet activated a proinflammatory response, as indicated by increases in plasma C-reactive protein and interleukin-6, and decreases in interleukin-10 (148). In another laboratory trial, lifelong sedentary behavior in mice led to accelerated muscle mitochondrial dysfunction and increased levels of mitochondrial oxidative damage (149).…”