Development of skeletal muscle fibrosis in a rodent model of cancer cachexia.

Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes.

Effects of PGC-1α overexpression on the myogenic response during skeletal muscle regeneration.

The ability of skeletal muscle to regenerate from injury is crucial for locomotion, metabolic health, and quality of life. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1A) is a transcriptional coactivator required for mitochondrial biogenesis. Increased mitochondrial biogenesis is associated with improved muscle cell differentiation, however PGC1A's role in skeletal muscle regeneration following damage requires further investigation.

The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration.

Diet-induced obesity has previously been shown to occur with the concomitant rise in the expression of proinflammatory cytokines and increases in collagen deposition. While it has been known that the regenerative process of skeletal muscle is altered in obese mice following an acute muscle injury, we sought to examine differences in the expression of various markers of extracellular matrix remodeling and repair. Our laboratory has previously reported an impaired inflammatory and protein synthetic signaling in these mice that may contribute negatively to the muscle regenerative process.

Sestrins regulate muscle stem cell metabolic homeostasis.

The health and homeostasis of skeletal muscle are preserved by a population of tissue-resident muscle stem cells (MuSCs) that maintain a state of mitotic and metabolic quiescence in adult tissues. The capacity of MuSCs to preserve the quiescent state declines with aging and metabolic insults, promoting premature activation and stem cell exhaustion. Sestrins are a class of stress-inducible proteins that act as antioxidants and inhibit the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling complex.

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs); however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing.

Cancer-induced Cardiac Atrophy Adversely Affects Myocardial Redox State and Mitochondrial Oxidative Characteristics.

Unlabelled: Cachexia presents in 80% of advanced cancer patients; however, cardiac atrophy in cachectic patients receives little attention. This cardiomyopathy contributes to increased occurrence of adverse cardiac events compared to age-matched population norms. Research on cardiac atrophy has focused on remodeling; however, alterations in metabolic properties may be a primary contributor.

Moderators of skeletal muscle maintenance are compromised in sarcopenic obese mice.

The purpose of this study was to determine whether sarcopenic obesity accelerates impairments in muscle maintenance through the investigation of cell cycle progression and myogenic, inflammatory, catabolic and protein synthetic signaling in mouse gastrocnemius muscles. At 4 weeks old, 24 male C57BL/6 mice were fed either a high fat diet (HFD, 60 % fat) or normal chow (NC, 17 % fat) for either 8-12 weeks or 21-23 months. At 3-4 months or 22-24 months the gastrocnemius muscles were excised.

Resolvin D1 supports skeletal myofiber regeneration via actions on myeloid and muscle stem cells.

Specialized proresolving mediators (SPMs) actively limit inflammation and expedite its resolution by modulating leukocyte recruitment and function. Here we profiled intramuscular lipid mediators via liquid chromatography-tandem mass spectrometry-based metabolipidomics following myofiber injury and investigated the potential role of SPMs in skeletal muscle inflammation and repair. Both proinflammatory eicosanoids and SPMs increased following myofiber damage induced by either intramuscular injection of barium chloride or synergist ablation-induced functional muscle overload.

Dissecting Murine Muscle Stem Cell Aging through Regeneration Using Integrative Genomic Analysis.

During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [MuSCs]), but in aging, MuSCs decrease in numbers and regenerative capacity. The transcriptional networks and epigenetic changes that confer diminished regenerative function in MuSCs as a result of natural aging are only partially understood.

Emerging molecular mediators and targets for age-related skeletal muscle atrophy.

The age-associated decline in muscle mass has become synonymous with physical frailty among the elderly due to its major contribution in reduced muscle function. Alterations in protein and redox homeostasis along with chronic inflammation, denervation, and hormonal dysregulation are all hallmarks of muscle wasting and lead to clinical sarcopenia in older adults. Reduction in skeletal muscle mass has been observed and reported in the scientific literature for nearly 2 centuries; however, identification and careful examination of molecular mediators of age-related muscle atrophy have only been possible for roughly 3 decades.

Denervation and senescence markers data from old rats with intrinsic differences in responsiveness to aerobic training.

The data described below is related to the manuscript "Late life maintenance and enhancement of functional exercise capacity in low and high responding rats after low intensity treadmill training" [1]. Rodents exhibit age-related declines in skeletal muscle function that is associated with muscle denervation and cellular senescence. Exercise training is a proven method to delay or even reverse some aging phenotypes, thus improving healthspan in the elderly.

Regulation of mitochondrial quality following repeated bouts of hindlimb unloading.

Muscle disuse impairs muscle quality and is associated with increased mortality. Little is known regarding additive effects of multiple bouts of disuse, which is a common occurrence in patients experiencing multiple surgeries. Mitochondrial quality is vital to muscle health and quality; however, to date mitochondrial quality control has not been investigated following multiple bouts of disuse.

Late life maintenance and enhancement of functional exercise capacity in low and high responding rats after low intensity treadmill training.

Unlabelled: Intrinsic exercise capacity is predictive of both lifespan and healthspan but whether adaptive exercise capacity influences the benefits achieved from aerobic training implemented later in life is not known.

Aim: To determine if exercise late in life provides any functional improvements or underlying beneficial biochemical adaptations in rats bred to have a high response to training (HRT rats) or little to no response to training (LRT rats).

Methods: Adult (11 months) and old (22 months) female LRT and HRT rats either remained sedentary (SED) or were exercised (EXER) on a treadmill 2-3 times/week at 60% of their initial maximum running speed and distance for 4 months.

Mitochondrial mRNA translation initiation contributes to oxidative metabolism in the myocardia of aged, obese mice.

Unlabelled: Being both advanced in age and obese each contribute to cardiac hypertrophy in a unique manner. Electron transport complexes I and IV are implicated in deficient electron transport during cardiomyopathies and contain the majority of protein subunits that are transcribed and translated by machinery localized within the mitochondria.

Purpose: To assess myocardial mt-mRNA translation factors in relation to mitochondrial content and mtDNA-encoded protein using a mouse model of aged obesity and to test the relationship of mt-mRNA translation initiation factor 2 (mtIF2) to oxidative capacity and the cellular oxidation-reduction (redox) state in cardiomyocytes.

Protein imbalance in the development of skeletal muscle wasting in tumour-bearing mice.

Background: Cancer cachexia occurs in approximately 80% of cancer patients and is a key contributor to cancer-related death. The mechanisms controlling development of tumour-induced muscle wasting are not fully elucidated. Specifically, the progression and development of cancer cachexia are underexplored.

Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice.

Cancer-cachexia (CC) is a wasting condition directly responsible for 20-40% of cancer-related deaths. The mechanisms controlling development of CC-induced muscle wasting are not fully elucidated. Most investigations focus on the postcachectic state and do not examine progression of the condition.

Cardiac hypertrophy in sarcopenic obese C57BL/6J mice is independent of Akt/mTOR cellular signaling.

Unlabelled: Sarcopenic obesity (SO) is the comorbidity of age-related muscle wasting and obesity. SO increases the risk of heart disease, but little is known about the cellular signaling in cardiac muscle of SO individuals.

Aim: The purpose of this study was to identify key cellular signaling alterations in cardiac muscle of sarcopenic obese mice.

Myeloid Cell Responses to Contraction-induced Injury Differ in Muscles of Young and Old Mice.

Myeloid cells play a critical role in regulating muscle degeneration and regeneration. Thus, alterations with aging in the myeloid cell response to muscle damage may affect the progression of the injury in old animals. We hypothesized that neutrophil levels remain elevated and that macrophage accumulation is reduced or delayed in injured muscles of old compared with young animals.

Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice.

Background: Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20-40% of cancer-related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia.

Autophagy activation, not peroxisome proliferator-activated receptor γ coactivator 1α, may mediate exercise-induced improvements in glucose handling during diet-induced obesity.

What is the central question of this study? What are the individual and combined effects of muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) overexpression and physical activity during high-fat feeding on glucose and exercise tolerance? What is the main finding and its importance? Our main finding is that muscle-specific PGC-1α overexpression provides no protection against lipid-overload pathologies nor does it enhance exercise adaptations. Instead, physical activity, regardless of PGC-1α content, protects against high-fat diet-induced detriments. Activation of muscle autophagy was correlated with exercise protection, suggesting that autophagy might be a mediating factor for exercise-induced protection from lipid overload.

Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size.

Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition.

Moderate physical activity promotes basal hepatic autophagy in diet-induced obese mice.

Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity.

The Akt/mTOR pathway: Data comparing young and aged mice with leucine supplementation at the onset of skeletal muscle regeneration.

The data described herein is related to the article "Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration" [1]. Aging is associated with a decreased ability of skeletal muscle to regenerate following injury. Leucine supplementation has been extensively shown, in young subjects, to promote protein synthesis during regeneration; however, the effects of leucine supplementation on the Akt/mTOR pathway in aged mice at the onset of muscle regeneration are not fully elucidated.

Recovery from volumetric muscle loss injury: A comparison between young and aged rats.

Termed volumetric muscle loss (VML), the bulk loss of skeletal muscle tissue either through trauma or surgery overwhelms the capacity for repair, leading to the formation of non-contractile scar tissue. The myogenic potential, along with other factors that influence wound repair are known to decline with age. In order to develop effective treatment strategies for VML injuries that are effective across a broad range of patient populations, it is necessary to understand how the response to VML injury is affected by aging.