The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

There is pressing need to understand the aging process to better cope with its associated physical and societal costs. The age-related muscle wasting known as sarcopenia is a major contributor to the problems faced by the elderly. By hindering mobility and reducing strength, it greatly diminishes independence and quality of life. In studying the factors that contribute to the development of sarcopenia, the focus is shifting to the study of disordered muscle anabolism. The abnormal response of muscle to previously well-established anabolic stimuli is known as anabolic resistance, and may be a key factor in the development and progression of sarcopenia. Factors such as age, obesity, inflammation, and lipotoxicity contribute to anabolic resistance, and have been studied either directly or indirectly in cell systems and whole animals. Understanding the physiologic and mechanistic basis of anabolic resistance could be the key to formulating new and targeted interventions that would ease the burden currently borne by the world’s aged population.

One of the most fundamental adaptive physiological events is the response of skeletal muscle to high-intensity resistance exercise, resulting in increased protein synthesis and ultimately larger muscle mass. However, muscle growth in response to contraction is attenuated in older humans. Impaired contractile-induced muscle growth may contribute to sarcopenia: the age-associated loss of muscle mass and function that is manifested by loss of strength, contractile capacity, and endurance. We hypothesized that the storage of ceramide would be increased in older individuals and this would be associated with increases in NFκB signaling and a decreased anabolic response to exercise. To test this hypothesis we measured ceramides at rest and anabolic and NFκB signaling after an acute bout of high-intensity resistance exercise in young and older males. Using lipidomics analysis we show there was a 156% increase in the accumulation of C16:0-ceramide (P < 0.05) and a 30% increase in C20:0-ceramide (P < 0.05) in skeletal muscle with aging, although there was no observable difference in total ceramide. C16:0-ceramide content was negatively correlated (P = 0.008) with lower leg lean mass. Aging was associated with a ~60% increase in the phosphorylation of the proinflammatory transcription factor NFκB in the total and nuclear cell fractions (P < 0.05). Furthermore, there was an attenuated activation of anabolic signaling molecules such as Akt (P < 0.05), FOXO1 (P < 0.05), and S6K1 (P < 0.05) after an acute bout of high-intensity resistance exercise in older males. We conclude that ceramide may have a significant role in the attenuation of contractile-induced skeletal muscle adaptations and atrophy that is observed with aging.

Purpose Describe the frequency and severity of knee ligament sprains diagnosed by MRI in athletes participating at the 2016 Summer Olympic Games, their association with certain sports and assess correlations with additional knee structural injury. Patients and Methods All knee MRIs performed in the Olympic Village and polyclinics during the 2016 Olympics were retrospectively, blindly reviewed for ligament sprains and associated knee injuries. In addition to the absence or presence of these abnormalities, athletes were stratified by age, gender and sport. Results 11,274 athletes participated in the 2016 Olympic Games: 113 athletes received at least one knee MRI with some having bilateral or repeat MRI on the same knee. Anterior cruciate and medial collateral ligament (ACL/MCL) sprains were most common, accounting for 32 of the 43 sprains (74.4%). Wrestling (10), hockey (7), athletics (7), and judo (5) accounted for over half of ligament sprains. ACL sprains showed a significant positive correlation with medial, lateral meniscal tears and bone contusions. The positive correlation between posterior cruciate ligament (PCL) sprains with MCL/lateral collateral ligament sprain, and popliteus tendon tear was statistically significant with 50% of total PCL sprains occurring in hockey. When athletes were stratified by gender, ligament sprains had a similar occurrence and distribution between men and women. Conclusion Knee ligament sprains, at the Rio 2016 Games, were most common in wrestling, hockey, athletics and judo with ACL and MCL sprains most frequent. Meniscal tears and bone contusions occurred often with ACL sprains. PCL sprains tended to be multi-ligamentous injuries. Sustained ligament sprains had similar occurrence between genders, while men had a peak incidence of sprains at a younger age and women at an older age.

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