Two weeks of one-leg immobilization decreases skeletal muscle respiratory capacity equally in young and elderly men

Gram, Martin; Vigelsø, Andreas; Yokota, Takashi; Hansen, Christina; Helge, Jørn Wulff; Hey-Mogensen, Martin; Dela, Flemming

doi:10.1016/j.exger.2014.08.013

Cited by 67 publications

(86 citation statements)

References 67 publications

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“…Although we refer to P IϩII as maximal coupled respiration, this may not be completely accurate. Indeed, in the current study, 36 -46% of P IϩII in skeletal muscle was insensitive to oligomycin (Table 2), which is in line with previously published data (10). This suggests that leak respiration may represent a proportion of P IϩII , at least in these experimental settings where supraphysiological concentrations of substrates are provided.…”

Section: Discussionsupporting

confidence: 93%

“…While numerous studies have reported a decline in skeletal muscle mitochondrial function with advancing age (1,3,5,15,17,20,30,31,33,35,37), there is disagreement in the literature (10,13,16,18,28). These discrepancies are likely attributable, in part, to heterogeneity in the physical activity levels and fitness of study cohorts.…”

Section: Discussionmentioning

confidence: 99%

“…Previous research suggests that skeletal muscle mitochondrial function declines with advancing age (1,3,5,17,30,31,33,35,37,38). Interestingly, though, others have shown that skeletal muscle mitochondrial respiration is similar in older men and women compared with cohorts of young men and women (10,13,16,18,28). Indeed, when matched for V O 2 max (18) or physical activity (16), skeletal muscle mitochondrial function is similar in young and older adults, suggesting that skeletal muscle mitochondrial dysfunction may not be an inherent component of senescence but rather a consequence of inactivity (27).…”

mentioning

confidence: 98%

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Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

Porter

Hurren

Cotter

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

121

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Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. Twenty-four young (28 ± 7 yr) and thirty-one older (62 ± 8 yr) adults were studied. Mitochondrial respiration was determined in permeabilized myofibers from the vastus lateralis after the addition of substrates oligomycin and CCCP. Thereafter, mitochondrial coupling control was calculated. Maximal coupled respiration (respiration linked to ATP production) was lower in muscle from older vs. young subjects (P < 0.01), as was maximal uncoupled respiration (P = 0.06). Coupling control in response to the ATP synthase inhibitor oligomycin was lower in older adults (P < 0.05), as was the mitochondria flux control ratio, coupled respiration normalized to maximal uncoupled respiration (P < 0.05). Calculation of respiratory function revealed lower respiration linked to ATP production (P < 0.001) and greater reserve respiration (P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

Porter

Hurren

Cotter

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

121

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“…) and changes in mitochondrial respiration and H 2 O 2 production (Gram et al . , ), leg function (e.g. leg lean mass, strength and muscle fibre type composition; Vigelsø et al .…”

Section: Methodsmentioning

confidence: 99%

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate‐intensity exercise in human skeletal muscle

Vigelsø

Gram

Dybboe

et al. 2016

The Journal of Physiology

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Key pointsr This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate-intensity exercise.r Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two-legged dynamic knee-extensor moderate-intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise.r Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise.r Using a combined whole-leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms.Abstract Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate-intensity exercise in young (n = 17; 23 ± 1 years old) and older men (n = 15; 68 ± 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two-legged isolated knee-extensor exercise at 20 ± 1 W (ß50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl-CoA carboxylase 2 and AMP-activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane-associated fatty acid binding protein and AMPKγ3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole-leg and molecular differences in fatty acid mobilization could explain the age-and immobilization-induced IMTG accumulation.

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“…Mitochondrial respiration was measured using permeabilized rat cardiomyocytes as previously described [34]. Complex I-linked state 3 respiration was assessed with malate (5 mM), glutamate (10 mM) and a saturating concentration of ADP (5 mM).…”

Section: Measurement Of Mitochondrial Respirationmentioning

confidence: 99%

The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes

Mizushima

Takahashi

Watanabe

et al. 2016

Journal of Molecular and Cellular Cardiology

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A failing heart shows severe energy insufficiency, and it is presumed that this energy shortage plays a critical role in the development of cardiac dysfunction. However, little is known about the mechanisms that cause energy metabolic alterations in the failing heart. Here, we show that the novel RING-finger protein 207 (RNF207), which is specifically expressed in the heart, plays a role in cardiac energy metabolism. Depletion of RNF207 in neonatal rat cardiomyocytes (NRCs) leads to a reduced cellular concentration of adenosine triphosphate (ATP) and mitochondrial dysfunction.Consistent with this result, we observed here that the expression of RNF207 was significantly reduced in mice with common cardiac diseases including heart failure.Intriguingly, proteomic approaches revealed that RNF207 interacts with the voltage-dependent anion channel (VDAC), which is considered to be a key regulator of mitochondria function, as an RNF207-interacting protein. Our findings indicate that RNF207 is involved in ATP production by cardiomyocytes, suggesting that RNF207 plays an important role in the development of heart failure.3 Highlights l RNF207 is specifically expressed in the heart. l RNF207 enhances activity of the tricarboxylic acid cycle in cardiomyocytes.l RNF207 directly interacts with VDAC1 through its coiled-coil domain.l Heart failure significantly reduces the expression of RNF207 in mice.4

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Two weeks of one-leg immobilization decreases skeletal muscle respiratory capacity equally in young and elderly men

Cited by 67 publications

References 67 publications

Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate‐intensity exercise in human skeletal muscle

The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes

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