Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging

Mansouri, Abdellah; Muller, Florian L.; Liu, Yuhong; Ng, Rainer; Faulkner, John A.; Hamilton, Michelle L.; Richardson, Arlan; Huang, Ting; Epstein, Charles J.; Remmen, Holly Van

doi:10.1016/j.mad.2005.11.004

Cited by 199 publications

(182 citation statements)

References 42 publications

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“…The reaction started upon the addition of Amplex Red reagent (100 μmol/l) and horseradish peroxidase (2 U/ml). Superoxide dismutase (100 U/ml) was added to the buffer to ensure complete conversion of superoxide to H 2 O 2 and to prevent the superoxide radical from interacting with the horseradish peroxidase [28].…”

Section: Methodsmentioning

confidence: 99%

Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice

et al. 2012

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Aims/hypothesis High-fat, high-sucrose diet (HF)-induced reactive oxygen species (ROS) levels are implicated in skeletal muscle insulin resistance and mitochondrial dysfunction. Here we investigated whether mitochondrial ROS sequestering can circumvent HF-induced oxidative stress; we also determined the impact of any reduced oxidative stress on muscle insulin sensitivity and mitochondrial function. Methods The Skulachev ion (plastoquinonyl decyltriphenylphosphonium) (SkQ), a mitochondria-specific antioxidant, was used to target ROS production in C2C12 muscle cells as well as in HF-fed (16 weeks old) male C57Bl/6 mice, compared with mice on low-fat chow diet (LF) or HF alone. Oxidative stress was measured as protein carbonylation levels. Glucose tolerance tests, glucose uptake assays and insulin-stimulated signalling were determined to assess muscle insulin sensitivity. Mitochondrial function was determined by high-resolution respirometry. Results SkQ treatment reduced oxidative stress in muscle cells (−23% p<0.05), but did not improve insulin sensitivity and glucose uptake under insulin-resistant conditions. In HF mice, oxidative stress was elevated (56% vs LF p<0.05), an effect completely blunted by SkQ. However, HF and HF+SkQ mice displayed impaired glucose tolerance (AUC HF up 33%, p<0.001; HF+SkQ up 22%; p<0.01 vs LF) and disrupted skeletal muscle insulin signalling. ROS sequestering did not improve mitochondrial function. Conclusions/interpretation SkQ treatment reduced muscle mitochondrial ROS production and prevented HF-induced oxidative stress. Nonetheless, whole-body glucose tolerance, insulin-stimulated glucose uptake, muscle insulin signalling and mitochondrial function were not improved. These results suggest that HF-induced oxidative stress is not a prerequisite for the development of muscle insulin resistance.

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Section: Methodsmentioning

confidence: 99%

Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice

et al. 2012

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“…However, studies have reported that the mCAT tg model exhibits similar fibrosis levels and loss of muscle fibre size to age‐matched old wild‐type (WT) mice,32 indicating that reduced mitochondrial oxidative damage and improved mitochondrial function failed to rescue age‐associated muscle wasting. Similarly, heterozygous knockout of MnSOD241, 266, 267, 268, 269 and conditional knockout of MnSOD targeted to type IIB skeletal muscle fibres25, 270 showed no major effect on age‐related loss of muscle mass and structural changes. However, both these models showed mitochondrial functional deficits associated with elevated mitochondrial oxidative damage25, 266, 269 and reduced skeletal muscle aerobic capacity,265, 270 which support a role for MnSOD in regulating mitochondrial function and, subsequently, the aerobic capacity of skeletal muscle.…”

Section: Non‐enzymatic Key Antioxidants That Contribute To the Maintementioning

confidence: 97%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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“…In higher eukaryotes, damaged organelles and proteins accumulate in long-lived postmitotic tissues, such as skeletal muscles, heart, liver, and brain (Schmucker 2005;Chaudhary et al 2011;Szweda et al 2003). Cells in these aging organs contain increased levels of damaged and dysfunctional cellular components with age: for example, neurons, astrocytes, microglia, hepatocytes, and cardiomyocytes accumulate lipofuscin deposits and other protein aggregates (Landfield et al 1981;Salminen et al 2011;Vaughan and Peters 1974;Frenzel and Feimann 1984;Schmucker and Sachs 2002); rhabdomyocytes accumulate mitochondria with oxidized bases in their DNA, reduced activity, and increased production of reactive oxygen species (Mansouri et al 2006); and cardiac myocytes accumulate impaired mitochondria with increased fragmentation of mitochondrial DNA (Frenzel and Feimann 1984;Ozawa 1998).…”

mentioning

confidence: 99%

p62/SQSTM1 at the interface of aging, autophagy, and disease

Bitto

Lerner

Nacarelli

et al. 2014

AGE

120

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Advanced age is characterized by increased incidence of many chronic, noninfectious diseases that impair the quality of living of the elderly and pose a major burden on the healthcare systems of developed countries. These diseases are characterized by impaired or altered function at the tissue and cellular level, which is a hallmark of the aging process. Age-related impairments are likely due to loss of homeostasis at the cellular level, which leads to the accumulation of dysfunctional organelles and damaged macromolecules, such as proteins, lipids, and nucleic acids. Intriguingly, aging and age-related diseases can be delayed by modulating nutrient signaling pathways converging on the target of rapamycin (TOR) kinase, either by genetic or dietary intervention. TOR signaling influences aging through several potential mechanisms, such as autophagy, a degradation pathway that clears the dysfunctional organelles and damaged macromolecules that accumulate with aging. Autophagy substrates are targeted for degradation by associating with p62/SQSTM1, a multidomain protein that interacts with the autophagy machinery. p62/SQSTM1 is involved in several cellular processes, and its loss has been linked to accelerated aging and to age-related pathologies. In this review, we describe p62/SQSTM1, its role in autophagy and in signaling pathways, and its emerging role in aging and age-associated pathologies. Finally, we propose p62/ SQSTM1 as a novel target for aging studies and ageextending interventions.

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Alterations in mitochondrial function, hydrogen peroxide release and oxidative damage in mouse hind-limb skeletal muscle during aging

Cited by 199 publications

References 42 publications

Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice

Targeting of mitochondrial reactive oxygen species production does not avert lipid-induced insulin resistance in muscle tissue from mice

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

p62/SQSTM1 at the interface of aging, autophagy, and disease

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