The Effect of Aging on Human Skeletal Muscle Mitochondrial and Intramyocellular Lipid Ultrastructure

Crane, Justin D.; Devries, Michaela C.; Safdar, Adeel; Hamadeh, Mazen J.; Tarnopolsky, Mark A.

doi:10.1093/gerona/glp179

Cited by 215 publications

(192 citation statements)

References 40 publications

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“…In white muscle, moreover, subsarcolemmal mitochondria were rarely observed, while intermyofibrillar mitochondria appeared highly organised in doublets (Fig. 4c) flanking the Z-lines, as has been seen by others [26]. Despite the scarcity of white muscle subsarcolemmal and intermyofibrillar mitochondria, these, when detected, did not differ in size in the two subcellular regions of lean or obese animals (Fig.…”

Section: Mitochondrial Size and Densitysupporting

confidence: 77%

Subcellular lipid droplet distribution in red and white muscles in the obese Zucker rat

et al. 2011

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Aims/hypothesis Little is known about the subcellular distribution of lipids in insulin-resistant skeletal muscle. However, it has recently been suggested that lipid accumulation in the subsarcolemmal region directly contributes to insulin resistance. Therefore we hypothesised that regional differences in lipid distribution in insulin-resistant muscle may be mediated by: (1) a reduction in fatty acid trafficking into mitochondria; and/or (2) a regional increase in the enzymes regulating lipid synthesis. Methods Transmission electron microscopy was used to quantify lipid droplet and mitochondrial abundance in the subsarcolemmal and intermyofibrillar compartments in red and white muscles from lean and obese Zucker rats. To estimate rates of lipid trafficking into mitochondria, the metabolic fate of radiolabelled palmitate was determined. Key enzymes of triacylglycerol synthesis were also determined in each subcellular region. Results Subsarcolemmal-compartmentalised lipids represented a small absolute fraction of the overall lipid content in muscle, as regardless of fibre composition (red/white) or phenotype (lean/obese), lipid droplets were more prevalent in the intermyofibrillar region, whereas insulin-resistant white muscles were devoid of subsarcolemmal-compartmentalised lipid droplets. While, in obese animals, lipid droplets accumulated in both subcellular regions, in red muscle of these animals lipids only appeared to be trafficked away from intermyofibrillar mitochondria, a process that cannot be explained by regional differences in the abundance of triacylglycerol esterification enzymes. Conclusions/interpretation Lipid accumulation in the subsarcolemmal region is not necessary for insulin resistance. In the intermyofibrillar compartment, the diversion of lipids away from mitochondria in insulin-resistant animals probably contributes to lipid accumulation in this subcellular area.

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Section: Mitochondrial Size and Densitysupporting

confidence: 77%

Subcellular lipid droplet distribution in red and white muscles in the obese Zucker rat

et al. 2011

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“…The subcellular localization of mitochondria and the overall 2538 Journal of Cell Science 123 (15) Journal of Cell Science mitochondrial network in multinucleated muscle fibers are tightly controlled by mitochondrion-shaping proteins, and an imbalance in mitochondrial fusion and fission dynamics probably impairs their function and contributes to the age-related loss of muscle. Indeed, it has recently been shown that the expression of Mfn2 and Drp1 genes is reduced in the skeletal muscle of aging individuals (Crane et al, 2010). Furthermore, the role of mitochondrionshaping proteins has recently been investigated in mice with a muscle-specific deficiency in Fis1 and Drp: diminished mitochondrial fission was associated with reduced muscle atrophy and attenuated activation of atrophy-related genes during fasting (Romanello et al, 2010).…”

Section: A Synthesis: Linking Mitochondrial Dynamics and Agingmentioning

confidence: 99%

New insights into the role of mitochondria in aging: mitochondrial dynamics and more

Seo

Joseph

Dutta

et al. 2010

Journal of Cell Science

465

366

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SummaryA decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders. A deeper understanding of the intricate nature of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in several key pathologies associated with aging. Indeed, a recent wave of studies has demonstrated the pleiotropic role of fusion and fission proteins in numerous cellular processes, including mitochondrial metabolism, redox signaling, the maintenance of mitochondrial DNA and cell death. Additionally, mitochondrial fusion and fission, together with autophagy, have been proposed to form a quality-maintenance mechanism that facilitates the removal of damaged mitochondria from the cell, a process that is particularly important to forestall aging. Thus, dysfunctional regulation of mitochondrial dynamics might be one of the intrinsic causes of mitochondrial dysfunction, which contributes to oxidative stress and cell death during the aging process. In this Commentary, we discuss recent studies that have converged at a consensus regarding the involvement of mitochondrial dynamics in key cellular processes, and introduce a possible link between abnormal mitochondrial dynamics and aging. Journal of Cell Science (Chen and Chan, 2009). However, the relevance of mitochondrial fusion and fission to underlying mechanisms of aging has not been fully appreciated, in part because the molecular events that underlie the aging process have not yet been completely elucidated. In this Commentary, we discuss current knowledge of mitochondrial dynamics, structure and function in relation to key cellular events, including mitochondrial biogenesis, mtDNA homeostasis, autophagy and cell death. By providing a basic overview of mitochondrial fusion and fission events and their general function in these crucial biological processes during normal stable environmental conditions, we hope to portray how alterations in mitochondrial dynamics can contribute to the mitochondrial dysfunction that is commonly associated with aging. Mechanisms underlying mitochondrial dynamicsMitochondria are highly complex and dynamic organelles that can alter their organization, shape and size, depending on intracellular and extracellular signals (Bereiter-Hahn and Voth, 1994;Rube and van der Bliek, 2004). Mitochondria undergo a continuous cycle of fusion and fission, and the balance between these opposing events determines the morphology of the organelle (Chen and Chan, 2004) (Fig. 2). Whereas decreased fusion can result in mitochondrial fragmentation because of excessive fission, decreased fission can generate long and highly interconnected mitochondria (Sesaki and Jensen, 1999).During the past decade, various cellular components have been identified as key mediators of mitochondrial fusion and fission in yeast (Hoppins et al., 2007;Merz et al., 2007;Okamoto and Shaw, 2005). The...

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“…Older adults have larger IMCL droplets, higher content in the subsarcolemmal area, fewer mitochondria, and a lower proportion of IMCL in contact with mitochondria compared with IMCL occurring in young skeletal muscle. These factors likely contribute to agerelated reductions in mitochondrial function and oxidative metabolism [63]. Magnetic resonance spectroscopy studies have shown that IMCL levels vary with insulin sensitivity and obesity, which is a common clinical picture in the older adult, and that inactivity combined with overconsumption of fat can have detrimental effects on muscular insulin sensitivity [64].…”

Section: Aging Skeletal Musclementioning

confidence: 99%

The Pleiotropic Effect of Physical Exercise on Mitochondrial Dynamics in Aging Skeletal Muscle

Barbieri¹,

Agostini²,

Polidori³

et al. 2016

Clinical Nutrition and Aging

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Decline in human muscle mass and strength (sarcopenia) is one of the principal hallmarks of the aging process. Regular physical exercise and training programs are certain powerful stimuli to attenuate the physiological skeletal muscle alterations occurring during aging and contribute to promote health and well-being. Although the series of events that led to these muscle adaptations are poorly understood, the mechanisms that regulate these processes involve the "quality" of skeletal muscle mitochondria. Aerobic/endurance exercise helps to maintain and improve cardiovascular fitness and respiratory function, whereas strength/resistance-exercise programs increase muscle strength, power development, and function. Due to the different effect of both exercises in improving mitochondrial content and quality, in terms of biogenesis, dynamics, turnover, and genotype, combined physical activity programs should be individually prescribed to maximize the antiaging effects of exercise.

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The Effect of Aging on Human Skeletal Muscle Mitochondrial and Intramyocellular Lipid Ultrastructure

Cited by 215 publications

References 40 publications

Subcellular lipid droplet distribution in red and white muscles in the obese Zucker rat

Subcellular lipid droplet distribution in red and white muscles in the obese Zucker rat

New insights into the role of mitochondria in aging: mitochondrial dynamics and more

The Pleiotropic Effect of Physical Exercise on Mitochondrial Dynamics in Aging Skeletal Muscle

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