Mitochondrial Maintenance in Skeletal Muscle.

Skeletal muscle is one of the tissues with the highest range of variability in metabolic rate, which, to a large extent, is critically dependent on tightly controlled and fine-tuned mitochondrial activity. Besides energy production, other mitochondrial processes, including calcium buffering, generation of heat, redox and reactive oxygen species homeostasis, intermediate metabolism, substrate biosynthesis, and anaplerosis, are essential for proper muscle contractility and performance. It is thus not surprising that adequate mitochondrial function is ensured by a plethora of mechanisms, aimed at balancing mitochondrial biogenesis, proteostasis, dynamics, and degradation.

Molecular aspects of the exercise response and training adaptation in skeletal muscle.

Skeletal muscle plasticity enables an enormous potential to adapt to various internal and external stimuli and perturbations. Most notably, changes in contractile activity evoke a massive remodeling of biochemical, metabolic and force-generating properties. In recent years, a large number of signals, sensors, regulators and effectors have been implicated in these adaptive processes.

More than the clock: distinct regulation of muscle function and metabolism by PER2 and RORα.

Circadian rhythms, governed by the dominant central clock, in addition to various peripheral clocks, regulate almost all biological processes, including sleep-wake cycles, hormone secretion and metabolism. In certain contexts, the regulation and function of the peripheral oscillations can be decoupled from the central clock. However, the specific mechanisms underlying muscle-intrinsic clock-dependent modulation of muscle function and metabolism remain unclear.

Generation of allogeneic and xenogeneic functional muscle stem cells for intramuscular transplantation.

Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts.

Bioactive gelatin-sheets as novel biopapers to support prevascularization organized by laser-assisted bioprinting for bone tissue engineering.

Despite significant advances in the management of patients with oral cancer, maxillofacial reconstruction after ablative surgery remains a clinical challenge. In bone tissue engineering, biofabrication strategies have been proposed as promising alternatives to solve issues associated with current therapies and to produce bone substitutes that mimic both the structure and function of native bone. Among them, laser-assisted bioprinting (LAB) has emerged as a relevant biofabrication method to print living cells and biomaterials with micrometric resolution onto a receiving substrate, also called 'biopaper'.

Robust, Precise, and Deep Proteome Profiling Using a Small Mass Range and Narrow Window Data-Independent-Acquisition Scheme.

In recent years, a plethora of different data-independent acquisition methods have been developed for proteomics to cover a wide range of requirements. Current deep proteome profiling methods rely on fractionations, elaborate chromatography, and mass spectrometry setups or display suboptimal quantitative precision. We set out to develop an easy-to-use one shot DIA method that achieves high quantitative precision and high proteome coverage.

Molecular control of endurance training adaptation in male mouse skeletal muscle.

Skeletal muscle has an enormous plastic potential to adapt to various external and internal perturbations. Although morphological changes in endurance-trained muscles are well described, the molecular underpinnings of training adaptation are poorly understood. We therefore aimed to elucidate the molecular signature of muscles of trained male mice and unravel the training status-dependent responses to an acute bout of exercise.

Impaired age-associated mitochondrial translation is mitigated by exercise and PGC-1α.

Sarcopenia, the age-related loss of skeletal muscle mass and function, can dramatically impinge on quality of life and mortality. While mitochondrial dysfunction and imbalanced proteostasis are recognized as hallmarks of sarcopenia, the regulatory and functional link between these processes is underappreciated and unresolved. We therefore investigated how mitochondrial proteostasis, a crucial process that coordinates the expression of nuclear- and mitochondrial-encoded mitochondrial proteins with supercomplex formation and respiratory activity, is affected in skeletal muscle aging.

Effects of high-resistance wheel running on hallmarks of endurance and resistance training adaptations in mice.

Exercise effectively promotes and preserves cardiorespiratory, neuromuscular, metabolic, and cognitive functions throughout life. The molecular mechanisms underlying the beneficial adaptations to exercise training are, however, still poorly understood. To improve the mechanistic study of specific exercise training adaptations, standardized, physiological, and well-characterized training interventions are required.

The molecular athlete: exercise physiology from mechanisms to medals.

Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation, and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete.

PGC-1β modulates catabolism and fiber atrophy in the fasting-response of specific skeletal muscle beds.

Objective: Skeletal muscle is a pivotal organ for the coordination of systemic metabolism, constituting one of the largest storage site for glucose, lipids and amino acids. Tight temporal orchestration of protein breakdown in times of fasting has to be balanced with preservation of muscle mass and function. However, the molecular mechanisms that control the fasting response in muscle are poorly understood.

PGC-1α and MEF2 Regulate the Transcription of the Carnitine Transporter OCTN2 Gene in C2C12 Cells and in Mouse Skeletal Muscle.

OCTN2 (SLC22A5) is a carnitine transporter whose main function is the active transport of carnitine into cells. In skeletal muscle and other organs, the regulation of the SLC22A5 gene transcription has been shown to depend on the nuclear transcription factor PPAR-α. Due to the observation that the muscle OCTN2 mRNA level is maintained in PPAR-α knock-out mice and that PGC-1α overexpression in C2C12 myoblasts increases OCTN2 mRNA expression, we suspected additional regulatory pathways for SLC22A5 gene transcription.

Drugs, clocks and exercise in ageing: hype and hope, fact and fiction.

Ageing is a biological process that is linked to a functional decline, ultimately resulting in death. Large interindividual differences exist in terms of life- and healthspan, representing life expectancy and the number of years spent in the absence of major diseases, respectively. The genetic and molecular mechanisms that are involved in the regulation of the ageing process, and those that render age the main risk factor for many diseases are still poorly understood.

In-vivo assessment of retinal vessel diameters and observer variability in mice: A methodological approach.

Background: Central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents are predictive for cardiovascular and all-cause mortality in humans. The aim of this study was to investigate the inter- and intraobserver variability for the assessment of CRAE and CRVE in mice using fluorescein contrast enhancement as compared to crude analysis.

Methods: Three high quality images with (F) and without fluorescein (NF) of eight mice (type C57BL) were recorded and analysed by two independent experienced investigators to investigate interobserver variability.

Characterization of regulatory transcriptional mechanisms in hepatocyte lipotoxicity.

Non-alcoholic fatty liver disease is a continuum of disorders among which non-alcoholic steatohepatitis (NASH) is particularly associated with a negative prognosis. Hepatocyte lipotoxicity is one of the main pathogenic factors of liver fibrosis and NASH. However, the molecular mechanisms regulating this process are poorly understood.

Time to Train: The Involvement of the Molecular Clock in Exercise Adaptation of Skeletal Muscle.

Circadian rhythms regulate a host of physiological processes in a time-dependent manner to maintain homeostasis in response to various environmental stimuli like day and night cycles, food intake, and physical activity. Disruptions in circadian rhythms due to genetic mutations, shift work, exposure to artificial light sources, aberrant eating habits, and abnormal sleep cycles can have dire consequences for health. Importantly, exercise training efficiently ameliorates many of these adverse effects and the role of skeletal muscle in mediating the benefits of exercise is a topic of great interest.

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle.

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making "CR mimetics" of great interest. CR targets nutrient-sensing pathways centering on mTORC1.

andcharacterization of a novel tricalcium silicate-based ink for bone regeneration using laser-assisted bioprinting.

Grafts aside, current strategies employed to overcome bone loss still fail to reproduce native tissue physiology. Among the emerging bioprinting strategies, laser-assisted bioprinting (LAB) offers very high resolution, allowing designing micrometric patterns in a contactless manner, providing a reproducible tool to test ink formulation. To this date, no LAB associated ink succeeded to provide a reproduciblebone regeneration on a murine calvaria critical size defect model.

Interleukin-6 potentiates endurance training adaptation and improves functional capacity in old mice.

Background: Interventions to preserve functional capacities at advanced age are becoming increasingly important. So far, exercise provides the only means to counteract age-related decrements in physical performance and muscle function. Unfortunately, the effectiveness of exercise interventions in elderly populations is hampered by reduced acceptance and compliance as well as disuse complications.

Cell-assembled extracellular matrix (CAM): a human biopaper for the biofabrication of pre-vascularized tissues able to connect to the host circulation.

When considering regenerative approaches, the efficient creation of a functional vasculature, that can support the metabolic needs of bioengineered tissues, is essential for their survival after implantation. However, it is widely recognized that the post-implantation microenvironment of the engineered tissues is often hypoxic due to insufficient vascularization, resulting in ischemia injury and necrosis. This is one of the main limitations of current tissue engineering applications aiming at replacing significant tissue volumes.

The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations.

Exercise, in the form of endurance or resistance training, leads to specific molecular and cellular adaptions not only in skeletal muscles, but also in many other organs such as the brain, liver, fat or bone. In addition to direct effects of exercise on these organs, the production and release of a plethora of different signaling molecules from skeletal muscle are a centerpiece of systemic plasticity. Most studies have so far focused on the regulation and function of such myokines in acute exercise bouts.

PGC-1α regulates myonuclear accretion after moderate endurance training.

The transcriptional demands of skeletal muscle fibres are high and require hundreds of nuclei (myonuclei) to produce specialised contractile machinery and multiple mitochondria along their length. Each myonucleus spatially regulates gene expression in a finite volume of cytoplasm, termed the myonuclear domain (MND), which positively correlates with fibre cross-sectional area (CSA). Endurance training triggers adaptive responses in skeletal muscle, including myonuclear accretion, decreased MND sizes and increased expression of the transcription co-activator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).