Muscle Blood Flow and Mitochondrial Function: Influence of Aging

Terjung, Ronald L.; Zarzeczny, Ryszard; Yang, Harrison Hao

doi:10.1123/ijsnem.12.3.368

Cited by 26 publications

(27 citation statements)

References 38 publications

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“…30 Mitochondrial dysfunction is also linked to decreased muscle blood flow with aging. 39 Because eNOS reportedly modulates mitochondrial biogenesis, 26 eNOS upregulation may contribute to enhanced mitochondrial contents in muscles of E-DNIB mice. Furthermore, endurance exercise, which is considered to confer life-spanextending effects, enhances the expression of a mitochondrial sirtuin, SIRT3, in human subjects.…”

Section: Discussionmentioning

confidence: 99%

Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans

Hasegawa

Saitō²,

Ogihara³

et al. 2012

Circulation

144

102

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Background-Nuclear factor-B (NF-B) signaling plays critical roles in physiological and pathological processes such as responses to inflammation and oxidative stress. Methods and Results-To examine the role of endothelial NF-B signaling in vivo, we generated transgenic mice expressing dominant-negative IB under the Tie2 promoter/enhancer (E-DNIB mice). These mice exhibited functional inhibition of NF-B signaling specifically in endothelial cells. Although E-DNIB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet-or genetics-induced. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased and blood flow and mitochondrial content in muscle and active-phase locomotor activity were increased in E-DNIB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-B signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged life span. These antiaging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins. Conclusions-The endothelium plays important roles in obesity-and age-related disorders through intracellular NF-B signaling, thereby ultimately affecting life span. Endothelial NF-B signaling is a potential target for treating the metabolic syndrome and for antiaging strategies. (Circulation. 2012;125:1122-1133.)Key Words: inflammation Ⅲ insulin resistance Ⅲ oxidative stress Ⅲ NF-B N uclear factor-kappa B (NF-B) is a transcription factor regulating the gene expression of numerous cytokines, growth factors, adhesion molecules, and enzymes involved in a variety of pivotal cellular processes, including responses to inflammation and oxidative stress. 1 Without inflammatory stimuli, NF-B is maintained in the cytoplasm in a nonactivated form by association with an inhibitor subunit, IB. In response to activating stimuli, including tumor necrosis factor-␣ (TNF-␣), lipopolysaccharide, and other inflammatory cytokines, IB is phosphorylated by IB kinase ␤, resulting in proteolysis of IB. Consequently, a nuclear recognition site of NF-B is exposed, and NF-B is stimulated to move into the nucleus, resulting in mRNA expression of target genes, including inflammatory cytokines and adhesion molecules. 2 Editorial see p 1081 Clinical Perspective on p 1133Obesity is characterized by a state of chronic low-grade inflammation. 3 Oxidative stress is also widely recognized as being associated with various obesity-related disorders. 4 Insulin resistance is an important mechanism underlying obesity-related disorders, eg, diabetes mellitus, hyperlipidemia, and hypertension, collectively called the metabolic syndrome. 5,6 In these metabolic states, NF-B has been implicated in the processes of both inflammatory responses Correspondence to Hid...

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Section: Discussionmentioning

confidence: 99%

Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans

Hasegawa

Saitō²,

Ogihara³

et al. 2012

Circulation

144

102

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“…A review of muscle blood flow and aerobic capacity in healthy older people has demonstrated that the increase in muscle capillarization after endurance training would enhance oxygen and nutrient exchanges within the tissue by providing a larger surface area and shorter diffusion distance. 17 To the best of our knowledge, there has been no study that has examined calf muscle capillarization in adaptation to supervised treadmill-walking training in patients with IC. In the present study, we aimed to evaluate the effect of 12 weeks of supervised treadmill-walking training on muscle capillarization and the relationship between the changes in walking capacity and muscle capillarization in subjects with IC.…”

mentioning

confidence: 99%

Effects of Supervised Treadmill Walking Training on Calf Muscle Capillarization in Patients with Intermittent Claudication

Wang

Zhou²,

Bronks³

et al. 2008

Angiology

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The aim of this study was to evaluate the effects of supervised treadmill-walking training on the calf muscle capillarization in patients with intermittent claudication. The first 12-week period was a non-exercise, within-subject control stage and the second 12-week period was an exercise training stage. Calf muscle biopsy samples were obtained at baseline, pre-and post-exercise training. Functional capacities were measured after each biopsy. Eleven subjects completed all procedures. Their average age was (mean ± SD) 73.9 ± 5.5 years, resting ankle-to-brachial index (ABI) 0.57 ± 0.11 and post-exercise ABI 0.40 ± 0.14 at baseline. After exercise training, there was no significant change in calf muscle capillarization, though walking capacity and peak oxygen uptake were increased significantly. The difference between the pre-and post-training capillaries in contact with type IIx and IIa muscle fibers for each subject was significantly correlated with an improved pain-free walking time, r=0.69 and r=0.62 (both p<0.05), respectively. This finding suggests that the change in calf muscle capillarization might contribute to improved walking capacity following exercise training in subjects with intermittent claudication.

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“…It has been suggested previously [10] that alterations in skeletal muscle mitochondrial capacity, blood flow capacity and oxygen extraction capacity, all of which contribute to changes in maximal oxygen uptake associated with either physical inactivity (aging related) or exercise training. Moreover, the coordinated interplay between these parameters may play a role in limiting muscle oxygen uptake [10] .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the coordinated interplay between these parameters may play a role in limiting muscle oxygen uptake [10] . This may explain the lack of differences between the groups with regard to oxygen extraction ca- pacity.…”

Section: Discussionmentioning

confidence: 99%

What Maintains Energy Supply at Peak Aerobic Exercise in Trained and Untrained Older Men?

Sagiv

Goldhammer²,

Ben‐Sira³

et al. 2007

Gerontology

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Background: Aging-related changes occur mainly in the cardiopulmonary system and skeletal muscles, bringing about a reduction in physical performance. Consequently, maximal oxygen uptake (VO₂max) decreases. Objectives: The current study investigated exercise oxygen utilization during maximal aerobic exercise in trained and untrained elderly. Methods: Fifteen trained (59.3 ± 1.1 years) and 15 untrained (60.1 ± 1.1 years) elderly underwent a peak cardiopulmonary exercise test on a bicycle ergometer. Arterial O₂was defined from echocardiograph and venous oxygen content. Results: At rest, trained compared to untrained elderly had significantly (p < 0.05) higher values of end diastolic volume (108.1 ± 5.8 and 100.7 ± 6.2 ml, respectively) and stroke volume (68.1 ± 4.3 and 57.3 ± 6.5 ml, respectively), while heart rate (68.7 ± 9.3 and 81.3 ± 8.2 beats · min^–1, respectively), and mean arterial blood pressure (90.6 ± 6.9 and 95.4 ± 7.2 mm Hg, respectively) were significantly lower. At peak aerobic test, the trained elderly, compared to the untrained subjects, achieved significantly (p < 0.05) higher values of end diastolic volume (156.1 ± 8.2 and 134.1 ± 7.6 ml, respectively), stroke volume (123.0 ± 7.9 and 96.0 ± 4.8 ml, respectively), cardiac output (20.2 ± 1.5 and 15.0 ± 1.3 liters·min^–1, respectively) and oxygen uptake (42.1 ± 2.1 and 31.1 ± 2.4 ml·kg^–1·min^–1, respectively), while diastolic blood pressure (70.3 ± 5.6 and 77.5 ± 4.2 mm Hg, respectively) and total peripheral resistance [4.3 ± 0.8 and 5.9 ± 1.41 (dyn·s^–1·cm^–5)·10^–1, respectively], were significantly (p < 0.05) lower. Conclusions: The present study suggests that the differences between trained and untrained elderly in absolute oxygen uptake of the working muscles and peak power output at maximal exercise test are due to physical activity status. The higher aerobic capacity in the trained elderly is related to increased cardiovascular function and to a lesser extent to increased muscle mitochondria concentration and capillarity. Although untrained elderly have reduced maximal oxygen uptake at peak aerobic exercise, intrinsic regulation of mitochondrial function does not seem to be significantly altered because of aging associated physical inactivity. Therefore, untrained elderly can partially compensate for their lower cardiac output by increasing oxygen extraction to levels comparable with those of trained elderly.

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Muscle Blood Flow and Mitochondrial Function: Influence of Aging

Cited by 26 publications

References 38 publications

Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans

Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans

Effects of Supervised Treadmill Walking Training on Calf Muscle Capillarization in Patients with Intermittent Claudication

What Maintains Energy Supply at Peak Aerobic Exercise in Trained and Untrained Older Men?

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