Senescent hearts from male Ts65Dn mice exhibit preserved function but altered size and nicotinamide adenine dinucleotide pathway signaling.

Down syndrome (DS) is associated with congenital heart defects at birth, but cardiac function has not been assessed at older ages. We used the Ts65Dn mouse, a model of DS, to quantify heart structure and function with echocardiography in 18-mo male Ts65Dn and wild-type (WT) mice. Heart weight, nicotinamide adenine dinucleotide (NAD) signaling, and mitochondrial (citrate synthase) activity were investigated, as these pathways may be implicated in the cardiac pathology of DS.

Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.

Individuals with Down syndrome (Ds) are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs.

Minute ventilation during hypoxia is augmented with capsaicin supplementation in aged mice.

Capsaicin is an agonist for transient receptor potential vanilloid 1 (TRPV1), and acute injection results in an increased frequency and tidal volume in young rats. It is unknown how capsaicin influences breathing in aged mice. We tested the hypothesis that capsaicin supplementation would elicit an augmented pattern of breathing in old mice compared to controls.

Effects of Prolonged Dietary Curcumin Exposure on Skeletal Muscle Biochemical and Functional Responses of Aged Male Rats.

Oxidative stress resulting from decreased antioxidant protection and increased reactive oxygen and nitrogen species (RONS) production may contribute to muscle mass loss and dysfunction during aging. Curcumin is a phenolic compound shown to upregulate antioxidant defenses and directly quench RONS in vivo. This study determined the impact of prolonged dietary curcumin exposure on muscle mass and function of aged rats.

Functional and biochemical responses of skeletal muscle following a moderate degree of systemic iron loading in mice.

Excessive iron loading may cause skeletal muscle atrophy and weakness because of its free radical generating properties. To determine whether a clinically relevant degree of iron loading impairs skeletal muscle function, young male mice received injections of iron dextran (4 mg iron/200 µl) or 2 mM d-glucose (control) 5 days/week for 2 weeks ( n = 10/group). Systemic iron loading induced an approximate fourfold increase in the skeletal muscle nonheme iron concentration.

Plasma irisin is increased following 12 weeks of Nordic walking and associates with glucose homoeostasis in overweight/obese men with impaired glucose regulation.

Irisin is a myokine that is thought to be secreted in response to exercise that may help to prevent obesity and maintain normal glucose metabolism. In this study we investigated the associations between irisin and glucose homeostasis in middle-aged, overweight and obese men (n =  144) with impaired glucose regulation, and the impact of exercise training on these relationships. The participants underwent 12 weeks of resistance or aerobic (Nordic walking) exercise training three times per week, 60 minutes per session.

Quiet breathing in hindlimb casted mice.

The hindlimb casting model was developed to study skeletal muscle reloading following a period of unloading. It is unknown if ventilation parameters of mice are affected by the casting model. We tested the hypothesis that hindlimb casted mice have similar ventilatory patterns compared to mice with the casts removed.

Effects of long-term exposures to low iron and branched-chain amino acid containing diets on aging skeletal muscle of Fisher 344 × Brown Norway rats.

Aging skeletal muscle displays an altered iron status that may promote oxidative stress and sarcopenia. A diet containing low iron (LI) could reduce muscle iron status and attenuate age-related muscle atrophy. Supplemental branched-chain amino acids (BCAA) may also alleviate sarcopenia by promoting muscle protein synthesis and iron status improvement.

Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice.

Down syndrome (DS) is a genetic condition caused by the triplication of chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an underlying factor in the development of DS-related pathologies including muscle dysfunction.

Changes in cytokines, leptin, and IGF-1 levels in overtrained athletes during a prolonged recovery phase: A case-control study.

We investigated how cytokines are implicated with overtraining syndrome (OTS) in athletes during a prolonged period of recovery. Plasma IL-6, IL-10, TNF-α, IL-1β, adipokine leptin, and insulin like growth factor-1 (IGF-1) concentrations were measured in overtrained (OA: 5 men, 2 women) and healthy control athletes (CA: 5 men, 5 women) before and after exercise to volitional exhaustion. Measurements were conducted at baseline and after 6 and 12 months.

Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress.

Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e.

Aging-related changes in the iron status of skeletal muscle.

The rise in non-heme iron (NHI) concentration observed in skeletal muscle of aging rodents is thought to contribute to the development of sarcopenia. The source of the NHI has not been identified, nor have the physiological ramifications of elevated iron status in aged muscle been directly examined. Therefore, we assessed plantaris NHI and heme iron (HI) levels in addition to expression of proteins involved in iron uptake (transferrin receptor-1; TfR1), storage (ferritin), export (ferroportin; FPN), and regulation (iron regulatory protein-1 (IRP1) and -2 (IRP2)) of male F344xBN F1 rats (n=10/group) of various ages (8, 18, 28, 32, and 36 months) to further understand iron regulation in aging muscle.

Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition.

Persons with Down syndrome (DS) exhibit low muscle strength that significantly impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits muscle weakness in vivo and may be a useful model to examine DS-associated muscle dysfunction. Therefore, the purpose of this experiment was to directly assess skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms of DS-associated muscle weakness.

The senescent rat diaphragm does not exhibit age-related changes in caspase activities, DNA fragmentation, or myonuclear domain.

The diaphragm muscle is essential for normal ventilation and it is chronically active throughout the lifespan. In most skeletal muscles, aging is associated with increased oxidative stress and myofiber atrophy. Since the diaphragm maintains a unique chronic contractile activity, we hypothesized that these alterations would not occur in senescent diaphragms compared to young diaphragms.

Skeletal muscle adaptations following blood flow-restricted training during 30 days of muscular unloading.

This study evaluated the effectiveness of low-load resistance training with a blood flow restriction (LL(BFR)) to attenuate muscle loss and weakness after 30 days of unilateral lower limb suspension (ULLS). Sixteen subjects (ages 18-50 yr) underwent 30 days of ULLS. Measurements of muscle strength, cross-sectional area, and endurance on the knee extensors and plantar flexors were collected before and after ULLS.

Metallothionein deficiency leads to soleus muscle contractile dysfunction following acute spinal cord injury in mice.

Metallothionein (MT) is a small molecular weight protein possessing metal binding and free radical scavenging properties. We hypothesized that MT-1/MT-2 null (MT(-/-)) mice would display exacerbated soleus muscle atrophy, oxidative injury, and contractile dysfunction compared with the response of wild-type (WT) mice following acute spinal cord transection (SCT). Four groups of mice were studied: WT laminectomy, WT transection, MT(-/-) laminectomy (MT(-/-) lami), and MT(-/-) transection (MT(-/-) trans).

Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery.

Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions.

Neural deficits contribute to respiratory insufficiency in Pompe disease.

Pompe disease is a severe form of muscular dystrophy due to glycogen accumulation in all tissues, especially striated muscle. Disease severity is directly related to the deficiency of acid alpha-glucosidase (GAA), which degrades glycogen in the lysosome. Respiratory dysfunction is a hallmark of the disease, muscle weakness has been viewed as the underlying cause, and the possibility of an associated neural contribution has not been evaluated previously.

Apocynin attenuates diaphragm oxidative stress and protease activation during prolonged mechanical ventilation.

Objective: To investigate whether apocynin protects the diaphragm from wasting and oxidative stress during mechanical ventilation (MV).

Design: Prospective, randomized, controlled study.

Setting: Research laboratory.

Effects of acute administration of corticosteroids during mechanical ventilation on rat diaphragm.

Rationale: Mechanical ventilation is known to induce ventilator-induced diaphragm dysfunction. Patients submitted to mechanical ventilation often receive massive doses of corticosteroids that may cause further deterioration of diaphragm function.

Objectives: To examine whether the combination of 24 hours of controlled mechanical ventilation with corticosteroid administration would exacerbate ventilator-induced diaphragm dysfunction.

Plantaris muscle of aged rats demonstrates iron accumulation and altered expression of iron regulation proteins.

Increased free radical production and oxidative damage in ageing muscle may be a contributing factor to the development of sarcopenia. It has been suggested that the accumulation of iron may be an underlying factor in the development of oxidative stress in ageing tissues, including skeletal muscle. At present, however, the mechanisms responsible for ageing-associated muscle iron accumulation are unknown.

Diaphragmatic proteasome function is maintained in the ageing Fisher 344 rat.

The diaphragm is the most important inspiratory muscle in mammals and is essential for normal ventilation. Therefore, maintenance of diaphragm function is critical to overall health throughout the lifespan. Evidence indicates that the ubiquitin proteasome pathway (UPP) function is diminished in locomotor skeletal muscle of ageing animals, but the function of the UPP in the senescent diaphragm has not yet been studied.

Caspase-3 regulation of diaphragm myonuclear domain during mechanical ventilation-induced atrophy.

Rationale: Unloading the diaphragm via mechanical ventilation (MV) results in rapid diaphragmatic fiber atrophy. It is unknown whether the myonuclear domain (cytoplasmic myofiber volume/myonucleus) of diaphragm myofibers is altered during MV.

Objective: We tested the hypothesis that MV-induced diaphragmatic atrophy is associated with a loss of myonuclei via a caspase-3-mediated, apoptotic-like mechanism resulting in a constant myonuclear domain.

Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in rats.

Objective: Nondepolarizing neuromuscular blocking agents are commonly used in the intensive care setting, but they have occasionally been associated with development of myopathy. In addition, diaphragmatic atrophy and a reduction in diaphragmatic force were reported after short-term controlled mechanical ventilation in animal models. We hypothesized that infusion of rocuronium, an aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled mechanical ventilation would further alter diaphragm function and would enhance activation of the ubiquitin- proteasome pathway.

Diaphragmatic nitric oxide synthase is not induced during mechanical ventilation.

Mechanical ventilation (MV) is associated with diaphragmatic oxidative stress that contributes to both diaphragmatic atrophy and contractile dysfunction. However, the pathways responsible for oxidant production in the diaphragm during MV remain unknown. To address this issue, we tested the hypothesis that diaphragmatic nitric oxide synthase (NOS) activity is elevated during MV, resulting in nitration of diaphragmatic proteins.