The role of mitochondria in aging of skeletal muscle (original) (raw)
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Aging impairs skeletal muscle mitochondrial bioenergetic function
The journals of gerontology. Series A, Biological sciences and medical sciences, 2009
This study investigated the infl uence of age on the functional status of mitochondria isolated from skeletal muscle of C57BL/6 mice aged 3 and 18 months. We hypothesized that skeletal muscle mitochondria isolated from aged animals will exhibit a decreased respiratory function. Mitochondrial respiratory functional measures (ie, State 3 and 4 respiration, respiratory control ratio and number of nanomoles of ADP phosphorylated by nanomoles of O 2 consumed per mitochondrion) and biochemical markers of oxidative damage (aconitase activity, protein carbonyl derivatives, sulfhydryl groups, and malondialdehyde ) were measured in isolated mitochondrial suspensions. Along with traditional tests of mitochondrial function, an in vitro repetitive ADP-stimulation test was used to evaluate the mitochondrial capacity to reestablish the homeostatic balance between successive ADP stimulations. The number of mitochondria per mitochondrial suspension, calculated by transmission electron microscopy, was used to normalize functional and biochemical data. Our results confi rm the existence of an age-associated decline in mitochondrial function of mixed skeletal muscle, which is signifi cantly correlated with higher levels of mitochondrial oxidative damage. oxidative stress is a primary cause of age-related impairment in mitochondrial function.
Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
International Journal of Molecular Sciences
The maintenance of mitochondrial integrity is critical for muscle health. Mitochondria, indeed, play vital roles in a wide range of cellular processes, including energy supply, Ca2+ homeostasis, retrograde signaling, cell death, and many others. All mitochondria-containing cells, including skeletal muscle cells, dispose of several pathways to maintain mitochondrial health, including mitochondrial biogenesis, mitochondrial-derived vesicles, mitochondrial dynamics (fusion and fission process shaping mitochondrial morphology), and mitophagy—the process in charge of the removal of mitochondria though autophagy. The loss of skeletal muscle mass (atrophy) is a major health problem worldwide, especially in older people. Currently, there is no treatment to counteract the progressive decline in skeletal muscle mass and strength that occurs with aging, a process termed sarcopenia. There is increasing data, including our own, suggesting that accumulation of dysfunctional mitochondria contribut...
Medicine & Science in Sports & Exercise, 2008
Aging is associated with mitochondrial dysfunction, which leads to a decline in cellular function and the development of age-related diseases. Reduced skeletal muscle mass with aging appears to promote a decrease in mitochondrial quality and activity. Moreover, mito-Q4 chondrial dysfunction adversely affects the quality and quantity of skeletal muscle. During aging, physical exercise can cause beneficial adaptations to cellular energy metabolism in skeletal muscle, including alterations to mitochondrial content, protein, and biogenesis. Here, we briefly summarize current findings on the association between the aging process and impairment of mitochondrial function, including mitochondrial biogenesis and reactive oxygen species (ROS) in skeletal muscle. We also discuss the potential role of exercise in the improvement of aging-driven mitochondrial dysfunctions.
Skeletal Muscle Mitochondrial Energetic Efficiency and Aging
International Journal of Molecular Sciences, 2015
Aging is associated with a progressive loss of maximal cell functionality, and mitochondria are considered a key factor in aging process, since they determine the ATP availability in the cells. Mitochondrial performance during aging in skeletal muscle is reported to be either decreased or unchanged. This heterogeneity of results could partly be due to the method used to assess mitochondrial performance. In addition, in skeletal muscle the mitochondrial population is heterogeneous, composed of subsarcolemmal and intermyofibrillar mitochondria. Therefore, the purpose of the present review is to summarize the results obtained on the functionality of the above mitochondrial populations during aging, taking into account that the mitochondrial performance depends on organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP from the oxidation of fuels.
Aging effects on the skeletal muscle mitochondrial proteome
2008
Efeitos do envelhecimento no proteoma mitocondrial do músculo esquelético Aging effects on the skeletal muscle mitochondrial proteome Dissertação apresentada à Universidade de Aveiro para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Métodos Biomoleculares, realizada sob a orientação científica do
The journals of gerontology. Series A, Biological sciences and medical sciences, 2008
Several in vitro studies about age-associated skeletal muscle mitochondrial dysfunction are somewhat conflicting, and this might be related to different normalization procedures. The objective of this study was to normalize the functional and biochemical data per number of mitochondria present in a mitochondrial suspension. Functional and biochemical parameters were obtained in mitochondrial suspensions from murine skeletal muscle of different ages. Mitochondrial respiratory function was polarographically measured using a Clark-type oxygen electrode. Biochemical analyses included determination of citrate synthase (CS) activity and total protein content in the mitochondrial suspension. Electron microscopy analysis of the suspensions allowed calculation of the number of mitochondria per milligram of protein. Our results conclude that advanced age is associated with mitochondrial dysfunction; moreover, from the correlation between morphological and biochemical data, it is evident that CS activity in the mitochondrial suspensions is a more accurate marker of mitochondrial mass than is total protein content.
Journal of Translational Medicine
Skeletal muscle aging is associated with a decline in motor function and loss of muscle mass- a condition known as sarcopenia. The underlying mechanisms that drive this pathology are associated with a failure in energy generation in skeletal muscle, either from age-related decline in mitochondrial function, or from disuse. To an extent, lifelong exercise is efficacious in preserving the energetic properties of skeletal muscle and thus may delay the onset of sarcopenia. This review discusses the cellular and molecular changes in skeletal muscle mitochondria during the aging process and how different exercise modalities work to reverse these changes. A key factor that will be described is the efficiency of mitochondrial coupling—ATP production relative to O2 uptake in myocytes and how that efficiency is a main driver for age-associated decline in skeletal muscle function. With that, we postulate the most effective exercise modality and protocol for reversing the molecular hallmarks of...
Mitophagy in maintaining skeletal muscle mitochondrial proteostasis and metabolic health with ageing
The Journal of Physiology
Skeletal muscle is important for overall functionality and health. Ageing is associated with an accumulation of damage to mitochondrial DNA and proteins. In particular, damage to mitochondrial proteins in skeletal muscle, which is a loss of mitochondrial proteostasis, contributes to tissue dysfunction and negatively impacts systemic health. Therefore, understanding the mechanisms underlying the regulation of mitochondrial proteostasis and how those mechanisms change with age is important for the development of interventions to Joshua C. Drake obtained his PhD in 'Human Bioenergetics' from Colorado State University. He studied mechanisms of proteostatic maintenance in mouse models of slowed ageing as a member of the Translational Research in Aging and Chronic Disease Laboratory under the direction of Drs Karyn L. Hamilton and Benjamin F. Miller. He now works in the laboratory of Dr Zhen Yan studying exercise-mediated regulation of mitophagy in skeletal muscle, supported by an ADA post-doctoral fellowship. Zhen Yan is a Professor of Medicine, Pharmacology, Molecular Physiology and Biological Physics, and resident member of the Robert M. Berne Cardiovascular Research Centre at the University of Virginia School of Medicine. Trained as a physician scientist, he has developed a rigorous research programme using the state-of-the-art molecular and imaging technologies in a variety of animal models with a focus on mitochondrial quality control by exercise and the systemic health impact.
Mitochondrial Adaptations in Aged Skeletal Muscle: Effect of Exercise Training
Physiological Research, 2017
The aging process is associated with a decline in mitochondrial functions. Mitochondria dysfunction is involved in initiation and progression of many health problems including neuromuscular, metabolic and cardiovascular diseases. It is well known that endurance exercise improves mitochondrial function, especially in the elderly. However, recent studies have demonstrated that resistance training lead also to substantial increases in mitochondrial function in skeletal muscle. A comprehensive understanding of the cellular mechanisms involved in the skeletal muscle mitochondrial adaptations to exercise training in healthy elderly subjects, can help practitioners to design and prescribe more effective exercise trainings.
Mitochondrial energetics is impaired in vivo in aged skeletal muscle
Aging Cell, 2014
With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging-related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male Wistar rats by combining a modular control analysis approach with 31 P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness ('elasticity') of mitochondrial oxidative phosphorylation to contraction-induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging-related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.