Abstract
To determine whether mitochondrial dysfunction is causally related to muscle atrophy with aging, we examined respiratory capacity, H(2) O(2) emission, and function of the mitochondrial permeability transition pore (mPTP) in permeabilized myofibers prepared from four rat muscles that span a range of fiber type and degree of age-related atrophy. Muscle atrophy with aging was greatest in fast-twitch gastrocnemius (Gas) muscle (-38%), intermediate in both the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (Sol) muscles (-21%), and non-existent in adductor longus (AL) muscle (+47%). In contrast, indices of mitochondrial dysfunction did not correspond to this differential degree of atrophy. Specifically, despite higher protein expression for oxidative phosphorylation (oxphos) system in fast Gas and EDL, state III respiratory capacity per myofiber wet weight was unchanged with aging, whereas the slow Sol showed proportional decreases in oxphos protein, citrate synthase activity, and state III respiration. Free radical leak (H(2) O(2) emission per O(2) flux) under state III respiration was higher with aging in the fast Gas, whereas state II free radical leak was higher in the slow AL. Only the fast muscles had impaired mPTP function with aging, with lower mitochondrial calcium retention capacity in EDL and shorter time to mPTP opening in Gas and EDL. Collectively, our results underscore that the age-related changes in muscle mitochondrial function depend largely upon fiber type and are unrelated to the severity of muscle atrophy, suggesting that intrinsic changes in mitochondrial function are unlikely to be causally involved in aging muscle atrophy.
Highlights
Impairment in mitochondrial function is posited to play an important role in the aging-related loss of muscle mass known as sarcopenia (Hiona & Leeuwenburgh, 2008; Hepple, 2011)
Several mechanisms have been proposed to account for an accumulation of mitochondria with impaired function in aging muscle, including mitochondrial DNA damage (Wanagat et al, 2001; Hiona et al, 2010), reduced mitochondrial protein turnover resulting from both reduced mitochondrial degradation and reduced synthesis of new mitochondria (Rooyackers et al, 1996; Baker et al, 2006; Chabi et al, 2008; Ljubicic & Hood, 2009), and mitochondrial iron accumulation leading to an exacerbation of mitochondrial oxidative stress (Seo et al, 2008)
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 (Picard et al, 2011)
Summary
Impairment in mitochondrial function is posited to play an important role in the aging-related loss of muscle mass known as sarcopenia (Hiona & Leeuwenburgh, 2008; Hepple, 2011). 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 (Picard et al, 2011). Mitochondrial isolation markedly exaggerated the severity of mitochondrial dysfunction in severely atrophied aging muscle (Picard et al, 2010)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
