Influences of Age and Dietary Restriction on Gastrocnemius Electron Transport System Activities in Mice

Desai, Varsha G.; Weindruch, Richard; Hart, Ronald W.; Feuers, Ritchie J.

doi:10.1006/abbi.1996.0375

Cited by 102 publications

(80 citation statements)

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“…Previous results have shown that old rats display a decrease in skeletal muscle mitochondrial activities (31)(32)(33), and when SS and IMF mitochondria have been studied separately in the heart, the above decrease was found to be restricted to IMF organelles (22). In addition, we have previously found that an aging-induced decline in hepatic mitochondrial activity of complex II is already evident in 180-day-old rats (7), indicating that the liver is affected early by the aging process.…”

Section: Discussionmentioning

confidence: 93%

A Possible Link Between Skeletal Muscle Mitochondrial Efficiency and Age-Induced Insulin Resistance

et al. 2004

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The transition from young to adult age is associated with decreased insulin sensitivity. To investigate whether changes in skeletal muscle mitochondrial function could be involved in the development of insulin resistance, we measured the oxidative capacity and energetic efficiency of subsarcolemmal and intermyofibrillar mitochondria isolated from the skeletal muscle of 60-and 180-day-old rats. Mitochondrial efficiency was tested by measuring the degree of thermodynamic coupling and optimal thermodynamic efficiency, as well as mitochondrial proton leak, which was determined in both the absence (basal) and the presence (fatty acid induced) of palmitate. Serum glucose, insulin, and HOMA index were also measured. The results show that in adult rats, concomitant with increased HOMA index, skeletal muscle mitochondria display higher respiratory capacity and energy efficiency. In fact, thermodynamic coupling and optimal thermodynamic efficiency significantly increased and fatty acid-induced proton leak was significantly lower in the skeletal muscle mitochondria from adult than in younger rats. A deleterious consequence of increased mitochondrial efficiency would be a reduced utilization of energy substrates, especially fatty acids, leading to intracellular triglyceride accumulation and lipotoxicity, thus contributing to the onset of skeletal muscle insulin resistance. Diabetes 53: 2861-2866, 2004 I ncreasing age is associated with obesity and insulin resistance not only in humans but also in rodents (1-5). In fact, ad libitum-fed caged rats are a good animal model that simulates the situation (sedentary lifestyle and unrestricted diet) of people in the western world.It has been previously shown that age-induced insulin resistance in rats is already detectable at 4 months of age, concomitant to a rapid rise in fat mass, and does not further increase later in life (3). This early decrease in insulin sensitivity could in turn lead to the metabolic disturbance typical of old age.Our previous results also indicate that in the transition from postpubertal (60 days) to adult (180 days) age, rats display reduced sensitivity to the anorexic effect of leptin (6) and, at the cellular level, hepatic mitochondrial machinery shows some age-related biochemical impairment (7,8). From all the above findings, it can be deduced that adult rats can be considered a good experimental tool for studying the onset of the "aging" phenomenon.It has been postulated that defects in mitochondrial performance could contribute to the development of insulin resistance (9), and mitochondrial oxidative capacity has been considered a good predictor of insulin sensitivity (10). These suggestions are not surprising since control of mitochondrial respiration and oxidative phosphorylation is fundamental for the maintenance of cellular homeostasis. The above control is exerted at two levels, i.e., regulation of the rate of oxygen consumption and ATP production and regulation of oxidative phosphorylation efficiency (11). The main determinant of oxidative phosp...

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Section: Discussionmentioning

confidence: 93%

A Possible Link Between Skeletal Muscle Mitochondrial Efficiency and Age-Induced Insulin Resistance

et al. 2004

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“…On the other hand, several lines of evidence suggest that a final common mechanism by which life-extending mutations [44,45] and dietary restriction [46,47] increase life span entails reducing oxidative damage. Furthermore, dietary restriction reduces the activity of complexes I, III and IV [48]; ATP production is presumably maintained by elevation of the relative complex II function. Similarly, dietary restriction decreases the production of reactive oxygen species in complex I without reducing mitochondrial oxygen consumption or reducing the production of reactive oxygen species in complex II [49][50][51].…”

Section: Dietary Restriction May Increase Life Span By Reducing Oxidamentioning

confidence: 99%

Secrets of the lac Operon

Mobbs¹,

Mastaitis²,

Zhang³

et al. 2006

Interdisciplinary Topics in Gerontology

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Elevated blood glucose associated with diabetes produces progressive and apparently irreversible damage to many cell types. Conversely, reduction of glucose extends life span in yeast, and dietary restriction reduces blood glucose. Therefore it has been hypothesized that cumulative toxic effects of glucose drive at least some aspects of the aging process and, conversely, that protective effects of dietary restriction are mediated by a reduction in exposure to glucose. The mechanisms mediating cumulative toxic effects of glucose are suggested by two general principles of metabolic processes, illustrated by the lac operon but also observed with glucose-induced gene expression. First, metabolites induce the machinery of their own metabolism. Second, induction of gene expression by metabolites can entail a form of molecular memory called hysteresis. When applied to glucose-regulated gene expression, these two principles suggest a mechanism whereby repetitive exposure to postprandial excursions of glucose leads to an age-related increase in glycolytic capacity (and reduction in ␤-oxidation of free fatty acids), which in turn leads to an increased generation of oxidative damage and a decreased capacity to respond to oxidative damage, independent of metabolic rate. According to this mechanism, dietary restriction increases life span and reduces pathology by reducing exposure to glucose and therefore delaying the development of glucose-induced glycolytic capacity.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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SummaryTo 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.

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Influences of Age and Dietary Restriction on Gastrocnemius Electron Transport System Activities in Mice

Cited by 102 publications

References 0 publications

A Possible Link Between Skeletal Muscle Mitochondrial Efficiency and Age-Induced Insulin Resistance

A Possible Link Between Skeletal Muscle Mitochondrial Efficiency and Age-Induced Insulin Resistance

Secrets of the lac Operon

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

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