The Distinct Molecular and Cardiometabolic Characteristics of the Soleus and Slow Oxidative Muscle Enhancing Chronic Disease Prevention and Healthy Aging

The slow oxidative muscle phenotype, especially in the soleus muscle, is regulated by unique cellular regulatory mechanisms distinct from other muscle types. Not all muscles share the same molecular machinery essential for key processes like insulin sensitivity and the breakdown of atherogenic triglyceride-rich lipoproteins. Muscle phenotype determines the effectiveness of muscular activity to enhance chronic disease prevention and promote healthy aging/longevity.

For every animal studied, the soleus muscle stands out due to its distinct molecular and metabolic profile, as well as its specialized anatomical features. These characteristics make it a key endocrine regulator of metabolic homeostasis, particularly in aging. For example, the soleus plays a critical role in maintaining vascular function by sustaining high blood flow rates, regulating postprandial glucose uptake, and optimizing lipid metabolism for energy balance. Additionally, its resistance to fatigue supports prolonged contractile activity, essential for postural stability and locomotion. Notably, its gene expression profile aligns more closely with muscles such as the diaphragm, tongue, and extraocular muscles than with other lower leg muscles, highlighting its unique integrative function in metabolic and endocrine physiology.

Skeletal muscle can act as an endocrine organ by secreting numerous proteins, with evidence suggesting that the soleus may have a more robust secretory capacity than muscles dominated by fast glycolytic fibers. Beyond its metabolic contributions, the soleus plays a critical role in cardiovascular-endocrine interactions, actively enhancing local muscle blood flow during contractions and facilitating venous return against gravity. Much like the heart, its rhythmic contractions serve as a muscular blood pump, optimizing cardiac filling pressures and overall circulatory efficiency. In humans, the soleus is significantly larger relative to body weight than in other mammals, with a distinct pinnated muscle fiber architecture that enhances its strength and endurance.

Taken together, there is a strong rationale for fostering a special collection of cutting-edge articles that add to understanding the mechanisms by which slow oxidative muscle in general, and the soleus specifically, play a distinct role in sustaining good health over the lifespan, in part by prevention of cardiometabolic conditions like type 2 diabetes. Themes of interest, include, but are not limited to:

• The endocrine/secretory functions of skeletal muscle, with an emphasis on fiber type comparisons.
• The distinct molecular characteristics of slow oxidative muscle in general, with an emphasis on comparisons of regulatory mechanisms in the soleus with other muscles.
• Fiber-type dependent mechanisms impacting insulin sensitivity at rest and contractile activity dependent .
• The role of local contractile activity on the uptake and utilization of glucose and other blood-borne substrates.
• The impact of soleus activity on cardiovascular function.
• Interventions aimed at enhancing soleus muscle function to prevent/treat chronic diseases in humans.
• Studies on the role of the soleus in balance, ambulatory function, and fall prevention in aging populations.

This collection explores the unique role of slow oxidative muscle, particularly the soleus, in maintaining health and preventing chronic disease. By examining its distinct contributions, this special issue aims to provide a clearer, more comprehensive understanding of how the soleus functions as an altruistic muscle in promoting healthy aging and disease prevention.