Nutrition, Exercise, and Pharmaceutical Therapies for Sarcopenic Obesity

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength, with a risk of adverse outcomes such as physical disability, poor quality of life, and death. Sarcopenic obesity is defined as having both sarcopenia and obesity, a condition reported to be associated with a higher risk for adverse outcomes including functional disability, frailty, poor quality of life, longer hospitalization, and higher mortality rates. The definition and diagnostic criteria for sarcopenia have been described by several working groups on the disease; however, there is no standardized definition and diagnostic criteria for sarcopenic obesity. In this review, we summarize nutrition, exercise, and pharmaceutical therapies for counteracting sarcopenic obesity in humans. Although there are some pharmaceutical therapies for both sarcopenia (i.e., testosterone, growth hormone, ghrelin, and vitamin D) and obesity (orlistat, lorcaserin, phentermine-topiramate, and vitamin D), therapies combining nutrition and exercise remain the first-line choice for preventing and treating sarcopenic obesity. Resistance training combined with supplements containing amino acids are considered most effective for treating sarcopenia. Low-calorie, high-protein diets combined with aerobic exercise and resistance training are recommended for preventing and treating obesity. Therefore, nutrition therapies (low-calorie, high-protein diets, protein and amino acid supplementation) and exercise therapies (resistance training and aerobic exercise) would be expected to be the most effective option for preventing and treating sarcopenic obesity. In cases of severe sarcopenic obesity or failure to achieve muscle gain and weight loss through nutrition and exercise therapies, it is necessary to add pharmaceutical therapies to treat the condition

Novel Intriguing Strategies Attenuating to Sarcopenia

Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA) or ursolic acid, etc.) for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant

Sarcopenic Dysphagia as a New Concept

Dysphagia (swallowing difficulties) is a serious problem associated with malnutrition, dehydration, aspiration pneumonia, and death. Its well‐known causes include stroke, neuromuscular disease, and head and neck cancer, and these affect muscles and sensation during deglutition. In recent years, dysphagia due to sarcopenia (i.e. “sarcopenic dysphagia”) has been reported as a new concept. Sarcopenic dysphagia results from low swallowing and general skeletal muscle mass and strength. The characteristic changes in swallowing muscles occur primarily in oral and pharyngeal muscles along with other associated factors. With a rapidly aging population, the number of older adults with sarcopenic dysphagia is expected to increase. Therefore, it is necessary to investigate the pathophysiology and treatment strategies for sarcopenic dysphagia. In this chapter, we summarize previous studies related to sarcopenic dysphagia

Molecular Mechanisms for Age-Associated Mitochondrial Deficiency in Skeletal Muscle

The abundance, morphology, and functional properties of mitochondria decay in skeletal muscle during the process of ageing. Although the precise mechanisms remain to be elucidated, these mechanisms include decreased mitochondrial DNA (mtDNA) repair and mitochondrial biogenesis. Mitochondria possess their own protection system to repair mtDNA damage, which leads to defects of mtDNA-encoded gene expression and respiratory chain complex enzymes. However, mtDNA mutations have shown to be accumulated with age in skeletal muscle. When damaged mitochondria are eliminated by autophagy, mitochondrial biogenesis plays an important role in sustaining energy production and physiological homeostasis. The capacity for mitochondrial biogenesis has shown to decrease with age in skeletal muscle, contributing to progressive mitochondrial deficiency. Understanding how these endogenous systems adapt to altered physiological conditions during the process of ageing will provide a valuable insight into the underlying mechanisms that regulate cellular homeostasis. Here we will summarize the current knowledge about the molecular mechanisms responsible for age-associated mitochondrial deficiency in skeletal muscle. In particular, recent findings on the role of mtDNA repair and mitochondrial biogenesis in maintaining mitochondrial functionality in aged skeletal muscle will be highlighted

Sarcopenia and Age-Related Endocrine Function

Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia

Molecular Mechanisms Controlling Skeletal Muscle Mass

The interplay between multiple signaling pathways regulates the maintenance of skeletal muscle. Under physiological conditions, a network of interconnected signals serves to coordinate hypertrophic and atrophic inputs, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed “atrophy,” is a diagnostic feature of cachexia such as cancer, heart disease, and chronic obstructive pulmonary disease. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce post-injury regeneration. In this review, we summarize the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle

The Recent Understanding of the Neurotrophin's Role in Skeletal Muscle Adaptation

This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise) produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression). In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease