Skeletal muscle is the largest site for postprandial glucose uptake. Reduced muscle mass and quality impair glucose disposal and lipid oxidation, directly contributing to insulin resistance. Conversely, preserving muscle mass through physical activity enhances insulin sensitivity and plays a preventive role in the development of metabolic syndrome.

Skeletal muscle is critical for glucose uptake and glycogen storage. Reduced muscle mass and impaired mitochondrial function diminish glucose utilization, promoting hyperglycemia. Resistance training and muscle hypertrophy enhance GLUT4 expression and improve insulin sensitivity, making skeletal muscle a cornerstone in diabetes prevention and management.

Skeletal muscle promotes hepatic lipid clearance and improves insulin signaling, both of which are impaired in NAFLD. Sarcopenia exacerbates hepatic steatosis and inflammation by promoting systemic insulin resistance and decreasing lipid oxidation. Muscle mass preservation is associated with lower liver fat content and better metabolic outcomes.

Muscle contraction induces vasodilation through nitric oxide and prostaglandin release, improving vascular compliance. Regular physical activity enhances endothelial function and reduces arterial stiffness. Loss of skeletal muscle, particularly in sedentary individuals, is associated with impaired blood pressure regulation and increased hypertension risk.

Skeletal muscle indirectly supports cardiac rhythm stability through its role in electrolyte balance, metabolic control, and autonomic regulation. Muscle loss contributes to systemic inflammation and oxidative stress, which can destabilize cardiac electrophysiology. Maintaining muscle mass may protect against arrhythmic events, particularly in aging individuals.

Atherosclerosis is driven by systemic inflammation and dyslipidemia—both modulated by skeletal muscle activity. Myokines such as IL-6 (when released from muscle during exercise) have anti-inflammatory effects, contrasting with the pro-inflammatory IL-6 secreted from adipose tissue. Preserving muscle mass helps attenuate vascular inflammation and plaque progression.

Skeletal muscle acts as a metabolic sink for excess glucose and lipids, reducing atherogenic burden. Muscle-derived anti-inflammatory myokines modulate endothelial function and systemic inflammation. Muscle mass preservation is associated with improved lipid profiles, lower CRP levels, and reduced CAD incidence.

In heart failure with preserved ejection fraction, skeletal muscle dysfunction contributes to exercise intolerance and reduced quality of life. Impaired muscle oxygen extraction and mitochondrial dysfunction are central features. Muscle-preserving interventions improve peripheral oxygen utilization and reduce hemodynamic stress on the heart.

Skeletal muscle produces anti-inflammatory and anti-cachectic myokines that modulate tumor microenvironments and systemic metabolism. Loss of muscle mass facilitates cancer cachexia, a wasting syndrome that accelerates tumor progression. Muscle preservation supports treatment tolerance and may even influence tumor biology.

Muscle mass is a key determinant of treatment tolerance, chemotherapy metabolism, and immune competence in cancer patients. Sarcopenia is associated with higher toxicity rates, dose-limiting side effects, and reduced survival. Maintaining skeletal muscle supports anabolic signaling, mitigates catabolic stress, and improves overall prognosis.

Muscle wasting is a common extrapulmonary manifestation of COPD, associated with poor prognosis and decreased exercise tolerance. Skeletal muscle supports respiratory efficiency and systemic oxygen utilization. Muscle preservation improves ventilatory efficiency, reduces dyspnea, and enhances quality of life in COPD patients.

CKD is characterized by protein-energy wasting, where muscle catabolism is accelerated. Skeletal muscle plays a buffering role in nitrogen balance and acid-base homeostasis. Muscle preservation mitigates uremic toxicity, improves insulin sensitivity, and reduces systemic inflammation—key factors that influence CKD progression and mortality.

Skeletal muscle acts as a key modulator of immune competence. It provides amino acids necessary for the synthesis of immune proteins and supports the function of lymphocytes and macrophages. Furthermore, myokines exert anti-inflammatory effects that balance immune responses. Sarcopenia weakens this regulatory axis, increasing susceptibility to infections and impairing recovery from immune challenges.

In Parkinson's disease, motor symptoms are aggravated by muscle atrophy, which compromises gait, balance, and strength. Skeletal muscle supports mitochondrial function and neuromuscular communication. Exercise-induced myokines have been shown to promote dopaminergic neuron survival and slow motor decline.

Beyond Alzheimer's and Parkinson's, skeletal muscle plays a neuroprotective role in a range of neurodegenerative disorders. Muscle-secreted myokines such as irisin and cathepsin B enhance neuronal health and cognitive function. Physical activity preserves neuromuscular junctions and supports central nervous system resilience against progressive degeneration.

Skeletal muscle mass is intricately linked to cognitive health through its role in systemic inflammation and metabolic regulation. Myokines released during muscle contraction, such as irisin and BDNF, cross the blood-brain barrier and promote neurogenesis, synaptic plasticity, and amyloid clearance. Muscle loss (sarcopenia) has been associated with increased risk of Alzheimer's, likely due to reduced metabolic resilience and impaired glucose metabolism in the brain.

Low skeletal muscle mass is a strong independent predictor of all-cause mortality. Muscle tissue is not only essential for mobility and physical function but also serves as a critical reservoir for amino acids and metabolic substrates during illness or stress. Maintaining muscle mass helps preserve physiological reserve, delays frailty, and reduces the risk of early death from both chronic and acute diseases.