Lean mass preservation

Lean mass preservation refers to the therapeutic maintenance of skeletal muscle and other non-fat tissues during periods of significant weight loss, aging, or chronic illness (1). While it is not a single molecular target, it represents a critical clinical objective in drug development aimed at countering sarcopenia, cachexia, and the unintended muscle loss associated with intensive weight-loss therapies like GLP-1 receptor agonists (2). The physiological process involves balancing anabolic pathways, such as the IGF-1/Akt/mTOR axis, against catabolic pathways regulated by the ubiquitin-proteasome system and myostatin/activin signaling (3). Current therapeutic strategies target specific proteins like Myostatin (GDF-8), Activin receptors, and the Androgen Receptor to promote protein synthesis or inhibit muscle degradation (4). Preserving lean mass is essential for maintaining physical function, metabolic rate, and overall quality of life in patients with obesity or degenerative conditions (5).

Other names

Muscle mass maintenanceSkeletal muscle preservationMyoprotectionLean body mass (LBM) preservation

Lean mass preservation is typically achieved by inhibiting negative regulators of muscle growth (e.g., Myostatin/Activin A antagonism at the ACVR2B receptor) or by activating anabolic signaling pathways (e.g., Selective Androgen Receptor Modulation or Apelin receptor agonism).