Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic.

SARS-CoV-2 infection is often associated with severe inflammation, oxidative stress, hypoxia and impaired physical activity. These factors all together contribute to muscle wasting and fatigue. In addition, there is evidence of a direct SARS-CoV-2 viral infiltration into skeletal muscle. Aging is often characterized by sarcopenia or sarcopenic obesity These conditions are risk factors for severe acute COVID-19 and long-COVID-19 syndrome. From these observations we may predict a strong association between COVID-19 and decreased muscle mass and functions. While the relationship between physical inactivity, chronic inflammation, oxidative stress and muscle dysfunction is well-known, the effects on muscle mass of COVID-19-related hypoxemia are inadequately investigated. The aim of this review is to highlight metabolic, immunity-related and redox biomarkers potentially affected by reduced oxygen availability and/or muscle fatigue in order to shed light on the negative impact of COVID-19 on muscle mass and function. Possible countermeasures are also reviewed.

Physical capacities and leisure activities are related with cognitive functions in older adults.

BACKGROUND: This study aimed to evaluate the relationship between physical activity habits, physical performance and cognitive capacity in older adults' population of Italy and Slovenia. METHODS: Anthropometric characteristics and body composition bioelectrical impedance analysis were evaluated in 892 older adults (60-80 y). Aerobic capacity was measured using the 2-km walk test and handgrip and flexibility tests were performed. Physical activity habits and cognitive functions were evaluated by the Global-Physical-Activity-Questionnaires (GPAQ) and by Montreal-Cognitive-Assessment (MoCA) questionnaires, respectively. RESULTS: GPAQ scores were associated with lower BMI (r=-0.096; P=0.005), lower percentage of fat-mass (r=-0.138; P=0.001), better results in the 2-km walk test (r=-0.175; P=0.001) and a higher percentage of fat-free mass (r=0.138; P=0.001). We also evaluated that a higher MoCA Score correlates with age (r=-0.208; P=0.001), 2-km walk test (r=-0.166; P=0.001), waist-hip ratio (r=-0.200; P=0.001), resting heart-rate (r=-0.087; P=0.025) and heart-rate at the end of 2-km walk test (r=0.189; P=0.001). CONCLUSIONS: Older adults with a higher level of daily physical activity showed reduction in fat-mass and BMI, and higher aerobic fitness; these characteristics have a protection effect on cognitive function.

Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory Changes in Circulating TRAIL and Glutathione Redox Capacity.

In chronic diseases, hypoxia and physical inactivity are associated with atherosclerosis progression. In contrast, a lower mortality from coronary artery disease and stroke is observed in healthy humans residing at high altitude in hypoxic environments. Eleven young, male volunteers completed the following 10-day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and normoxic bed rest. Before intervention, subjects were evaluated in normoxic ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility simulating 4000 m of altitude. Following hypoxia, either in bed rest or ambulatory condition, markers of cardiometabolic risk shifted toward a more atherogenic pattern consisting of: (a) lower levels of total HDL cholesterol and HDL2 sub-fraction and decreased hepatic lipase; (b) activation of systemic inflammation, as determined by C-reactive protein and serum amyloid A; (c) increased plasma homocysteine; (d) decreased delta-5 desaturase index in cell membrane fatty acids, a marker of insulin sensitivity. Bed rest and hypoxia additively decreased total HDL and delta-5 desaturase index. In parallel to the pro-atherogenic effects, hypoxia activated selected anti-atherogenic pathways, consisting of increased circulating TNF-related apoptosis-inducing ligand (TRAIL), a protective factor against atherosclerosis, membrane omega-3 index and erythrocyte glutathione availability. Hypoxia mediated changes in TRAIL concentrations and redox glutathione capacity (i.e., GSH/GSSG ratio) were greater in ambulatory conditions (+34 ± 6% and +87 ± 31%, respectively) than in bed rest (+17 ± 7% and +2 ± 27% respectively). Hypoxia-induced cardiometabolic risk is blunted by moderate level of physical activity as compared to bed rest. TRAIL and glutathione redox capacity may contribute to the positive interaction between physical activity and hypoxia. Highlights: - Hypoxia and bed rest activate metabolic and inflammatory markers of atherogenesis. - Hypoxia and physical activity activate selected anti-atherogenic pathways. - Hypoxia and physical activity positive interaction involves TRAIL and glutathione.

Intermittent vs. continuous enteral feeding to prevent catabolism in acutely ill adult and pediatric patients.

PURPOSE OF REVIEW: In clinical management of acutely ill adults and children, continuous enteral feeding (CEF), being considered the most tolerable approach, in comparison to other temporal patterns of nutrient administration (i.e. intermittent, cyclic and bolus), is the most frequently applied method. However, uncertainties remain about the most efficient approach to counteract protein catabolism. RECENT FINDINGS: In critically ill adults, protein loss is mainly driven by increased protein breakdown whereas, in pediatric patients, acute illness is mainly characterized by blunted regulation of protein synthesis and stunted growth. Kinetic studies in fed adult volunteers indicate that protein synthesis can be stimulated for a limited period only. However, continuous feeding persistently improves protein balance through a sustained suppression of protein breakdown. This leads to the hypothesis that CEF could be more anticatabolic than intermittent enteral feeding (IEF) in these patients. Differently from adults, experimental models of acute disease in growing animals have consistently indicated that IEF can improve protein anabolism more efficiently than CEF, mainly through protein synthesis stimulation. The scarce number of clinical studies in acutely ill adults or pediatric patients, mostly performed with inadequate methodology, could not define the best approach to maintain protein balance. SUMMARY: There is a need for pragmatic studies to directly compare the protein anabolic action of CEF and IEF using accurate methodologies, such as stable isotopes of amino acids, in both adult and pediatric patients with acute illness.

What factors influence protein synthesis and degradation in critical illness?

PURPOSE OF REVIEW: The optimal approach to improve protein metabolism in critical illness is not yet fully defined. Here, we have summarized recent literature dealing with the main catabolic and anabolic factors influencing protein kinetics in acute hypercatabolic patients. RECENT FINDINGS: Protein/amino acid intake levels should be adapted to type and severity of illness, keeping in mind that energy overfeeding is associated with poor outcome. A number of anticatabolic nutraceuticals and drugs have been tested in acute patients. The encouraging results have been obtained with ß-hydroxy-ß-methylbutyrate, omega-3 fatty acids, oxandrolone, propranolol, and metformin. Their efficacy and lack of side-effects need to be confirmed. Physical therapy, including muscle electro-stimulation, appears a very promising intervention, both effective and safe. SUMMARY: Protein catabolism can be minimized in acute patients by adequate nutritional support, early mobilization, and, possibly, pharmacological and nutraceutical interventions. A combination of these strategies should be tested in randomized controlled trials.