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Background: As people age, physical impairments may have a deleterious role in skeletal muscles. Sarcopenia Clinical Practice Guidelines 2017 and the European Working Group on Sarcopenia in older people are two organizations that have published essential guidelines on the definition of “sarcopenia". Sarcopenia is a geriatric syndrome, characterized by skeletal muscle mass degeneration brought on by ageing, which lowers muscular function and quality. Moreover, sarcopenia can be classified as primary or age-associated sarcopenia and secondary sarcopenia. Also, secondary sarcopenia occurs when other diseases such as diabetes, obesity, cancer, cirrhosis, myocardial failure, chronic obstructive pulmonary disease, and inflammatory bowel disease also contribute to muscle loss. Furthermore, sarcopenia is linked with a high risk of negative outcomes, considering a gradual reduction in physical mobility, poor balance, and increased fracture risks which ultimately leads to poor quality of life. Objective: In this comprehensive review, we have elaborated on the pathophysiology, and various signaling pathways linked with sarcopenia. Also, discussed are the preclinical models and current interventional therapeutics to treat muscle wasting in older patients. Conclusion: In a nutshell, a comprehensive description of the pathophysiology, mechanisms, animal models, and interventions of sarcopenia. We also shed light on pharmacotherapeutics present in clinical trials which are being developed as potential therapeutic options for wasting diseases. Thus, this review could fill in the knowledge gaps regarding sarcopenia-related muscle loss and muscle quality for both researchers and clinicians.

(1) Background: Skeletal muscle atrophy is a common and debilitating condition associated with disease, bed rest, and inactivity. We aimed to investigate the effect of atenolol (ATN) on cast immobilization (IM)-induced skeletal muscle loss. (2) Methods: Eighteen male albino Wistar rats were divided into three groups: a control group, an IM group (14 days), and an IM+ATN group (10 mg/kg, orally for 14 days). After the last dose of atenolol, forced swimming test, rotarod test, and footprint analysis were performed, and skeletal muscle loss was determined. Animals were then sacrificed. Serum and gastrocnemius (GN) muscles were then collected, serum creatinine, GN muscle antioxidant, and oxidative stress levels were determined, and histopathology and 1H NMR profiling of serum metabolites were performed. (3) Results: Atenolol significantly prevented immobilization-induced changes in creatinine, antioxidant, and oxidative stress levels. Furthermore, GN muscle histology results showed that atenolol significantly increased cross-sectional muscle area and Feret’s diameter. Metabolomics profiling showed that glutamine-to-glucose ratio and pyruvate, succinate, valine, citrate, leucine, isoleucine, phenylalanine, acetone, serine, and 3-hydroxybutyrate levels were significantly higher, that alanine and proline levels were significantly lower in the IM group than in the control group, and that atenolol administration suppressed these metabolite changes. (4) Conclusions: Atenolol reduced immobilization-induced skeletal muscle wasting and might protect against the deleterious effects of prolonged bed rest.

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1β, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle 1H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret’s diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy.