Sarcopenia: Origins and Clinical Relevance

Rosenberg, Irwin H.

doi:10.1093/jn/127.5.990s

Cited by 1,847 publications

(1,110 citation statements)

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“…related bone wasting and increase in adiposity may occur not only from diminished peak-load-bearing capacity, but the dissolution of low-level signals caused by the sarcopenia that parallels these conditions (33).…”

Section: Discussionmentioning

confidence: 99%

Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals

Rubin¹,

Capilla²,

Luu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

238

198

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Obesity, a global pandemic that debilitates millions of people and burdens society with tens of billions of dollars in health care costs, is deterred by exercise. Although it is presumed that the more strenuous a physical challenge the more effective it will be in the suppression of adiposity, here it is shown that 15 weeks of brief, daily exposure to high-frequency mechanical signals, induced at a magnitude well below that which would arise during walking, inhibited adipogenesis by 27% in C57BL/6J mice. The mechanical signal also reduced key risk factors in the onset of type II diabetes, nonesterified free fatty acid and triglyceride content in the liver, by 43% and 39%, respectively. Over 9 weeks, these same signals suppressed fat production by 22% in the C3H.B6 -6T congenic mouse strain that exhibits accelerated age-related changes in body composition. In an effort to understand the means by which fat production was inhibited, irradiated mice receiving bone marrow transplants from heterozygous GFP ؉ mice revealed that 6 weeks of these low-magnitude mechanical signals reduced the commitment of mesenchymal stem cell differentiation into adipocytes by 19%, indicating that formation of adipose tissue in these models was deterred by a marked reduction in stem cell adipogenesis. Translated to the human, this may represent the basis for the nonpharmacologic prevention of obesity and its sequelae, achieved through developmental, rather than metabolic, pathways. mesenchymal stem cells ͉ obesity ͉ therapeutics ͉ diabetes ͉ vibration

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Section: Discussionmentioning

confidence: 99%

Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals

Rubin¹,

Capilla²,

Luu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

238

198

View full text Add to dashboard Cite

show abstract

“…Human aging is accompanied by a decline of skeletal muscle mass and strength, phenomena called sarcopenia and dynapenia, respectively (Manini & Clark, 2012; Rosenberg, 1997). It is estimated that up to 33% of elderly people suffer from age‐related muscle loss, the exact number depending on age and regional variation (Cruz‐Jentoft et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism

et al. 2017

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SummaryLoss of mitochondrial respiratory flux is a hallmark of skeletal muscle aging, contributing to a progressive decline of muscle strength. Endurance exercise alleviates the decrease in respiratory flux, both in humans and in rodents. Here, we dissect the underlying mechanism of mitochondrial flux decline by integrated analysis of the molecular network.Mice were given a lifelong ad libitum low‐fat or high‐fat sucrose diet and were further divided into sedentary and running‐wheel groups. At 6, 12, 18 and 24 months, muscle weight, triglyceride content and mitochondrial respiratory flux were analysed. Subsequently, transcriptome was measured by RNA‐Seq and proteome by targeted LC‐MS/MS analysis with 13C‐labelled standards. In the sedentary groups, mitochondrial respiratory flux declined with age. Voluntary running protected the mitochondrial respiratory flux until 18 months of age. Beyond this time point, all groups converged. Regulation Analysis of flux, proteome and transcriptome showed that the decline of flux was equally regulated at the proteomic and at the metabolic level, while regulation at the transcriptional level was marginal. Proteomic regulation was most prominent at the beginning and at the end of the pathway, namely at the pyruvate dehydrogenase complex and at the synthesis and transport of ATP. Further proteomic regulation was scattered across the entire pathway, revealing an effective multisite regulation. Finally, reactions regulated at the protein level were highly overlapping between the four experimental groups, suggesting a common, post‐transcriptional mechanism of muscle aging.

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“…Sarcopenia, the involuntary loss of skeletal muscle mass and function with age (Rosenberg, 1997), contributes significantly to frailty and causes a decline in quality of life. In humans, 30% of the muscle mass is lost between 20 and 80 years of age (Frontera et al ., 2000).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis and necrosis mediate skeletal muscle fiber loss in age‐induced mitochondrial enzymatic abnormalities

et al. 2015

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SummarySarcopenia, the age‐induced loss of skeletal muscle mass and function, results from the contributions of both fiber atrophy and loss of myofibers. We have previously characterized sarcopenia in FBN rats, documenting age‐dependent declines in muscle mass and fiber number along with increased fiber atrophy and fibrosis in vastus lateralis and rectus femoris muscles. Concomitant with these sarcopenic changes is an increased abundance of mitochondrial DNA deletion mutations and electron transport chain (ETC) abnormalities. In this study, we used immunohistological and histochemical approaches to define cell death pathways involved in sarcopenia. Activation of muscle cell death pathways was age‐dependent with most apoptotic and necrotic muscle fibers exhibiting ETC abnormalities. Although activation of apoptosis was a prominent feature of electron transport abnormal muscle fibers, necrosis was predominant in atrophic and broken ETC‐abnormal fibers. These data suggest that mitochondrial dysfunction is a major contributor to the activation of cell death processes in aged muscle fibers. The link between ETC abnormalities, apoptosis, fiber atrophy, and necrosis supports the hypothesis that mitochondrial DNA deletion mutations are causal in myofiber loss. These studies suggest a progression of events beginning with the generation and accumulation of a mtDNA deletion mutation, the concomitant development of ETC abnormalities, a subsequent triggering of apoptotic and, ultimately, necrotic events resulting in muscle fiber atrophy, breakage, and fiber loss.

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Sarcopenia: Origins and Clinical Relevance

Cited by 1,847 publications

References 1 publication

Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals

Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals

Running‐wheel activity delays mitochondrial respiratory flux decline in aging mouse muscle via a post‐transcriptional mechanism

Apoptosis and necrosis mediate skeletal muscle fiber loss in age‐induced mitochondrial enzymatic abnormalities

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