The Muscle Function Deficit Concept and Inflammaging

Abstract

Aging-related muscle dysfunction has been conceptualized through the model of sarcopenia, but it embraces several other characteristics, e.g., dynapenia, myosteatosis, and powerpenia. Our perspective reframes muscle aging from a different point of view, the Skeletal Muscle Function Deficit (SMFD), a unifying approach that integrates muscle quality and mass into a single functional definition. An SMFD score has been adopted in the InCHIANTI study against many geriatric outcomes, such as risk of disability, physical performance, hospitalizations and falls, and incidence of major diseases, highlighting its potential value as a primary indicator of muscle failure and/or of healthy aging. At the core of SMFD lies inflammaging, the chronic, low-grade, age-related inflammation, linking functional outcomes to muscular and neural aging. Inflammatory mediators alter the anabolic/catabolic balance, accelerate myosteatosis, impair neuromuscular junction, and influence denervation. These findings support the idea of a common pathway that links neuro-muscular deficit and inflammation, which simultaneously targets cortical motor circuits, spinal motor neurons, peripheral nerves, and muscle fibers. The SMFD approach facilitates early detection, risk stratification, and possible intervention for muscle deterioration with aging.