What is the Origin of Age-Related Anabolic Resistance?

This term evolved from early studies in geriatric medicine and exercise physiology that sought to explain why protein turnover rates declined with advancing age, even with adequate nutrient intake. The concept of "resistance" was borrowed from the established pathology of insulin resistance, applying the same principle of impaired cellular signaling to muscle protein synthesis. It highlights a critical target for longevity and healthy aging research.

What is the Mechanism of Age-Related Anabolic Resistance?

The primary mechanism involves defects at multiple points in the muscle protein synthesis pathway, particularly within the mTOR (mammalian Target of Rapamycin) signaling cascade. Aging muscle cells experience a reduced uptake of amino acids and an impaired activation of key regulatory proteins necessary to initiate translation. Furthermore, a chronic low-grade inflammation, known as inflammaging, contributes to the desensitization of muscle tissue to anabolic signals. Over time, this cumulative signaling impairment shifts the balance towards catabolism.

Age-Related Anabolic Resistance

Meaning

Age-Related Anabolic Resistance describes the physiological state in which aging tissues, primarily skeletal muscle, exhibit a diminished sensitivity and response to anabolic stimuli, such as amino acids, resistance exercise, and key growth hormones like insulin and testosterone. This resistance impairs the body’s ability to synthesize new proteins and repair tissue, leading directly to sarcopenia and a decline in metabolic health. It is a fundamental process underlying the loss of muscle mass and strength observed in older adults. Clinically, recognizing this resistance guides therapeutic interventions toward maximizing the diminished anabolic signaling pathways.