PART 1: THE MUSCLE PANIC IS MEASURING THE WRONG VARIABLE GLP-1 receptor agonists reduce lean mass. In DXA substudies, roughly 39% of the weight lost on semaglutide and 25% on tirzepatide was classified as lean mass. But lean mass is not synonymous with skeletal muscle. It also includes water, organs, connective tissue, and other fat-free compartments. The headline number is doing more work than it can bear. Still, it has birthed a genre: you’re melting your muscle, you’ll end up skinny-fat, you’re accelerating sarcopenia. That framing misses a crucial distinction: Mass and quality are different variables — and obesity is associated with damage to the second one. Obesity is associated with fewer efficient, fat-oxidizing Type I fibers, more fatigue-prone Type IIx fibers, intramuscular fat, and chronic low-grade inflammation. The result may be a large volume of tissue that is loud in the wrong signals and quiet in the right ones. High mass. Low signal. A large transmitter buried in static. A thin, sarcopenic 75-year-old and a 300-pound 40-year-old may therefore arrive at overlapping forms of muscle dysfunction and impaired immune surveillance. One has too little functional tissue. The other has abundant tissue of degraded signaling quality. Different routes. Overlapping destination. Aging and sarcopenia are also associated with altered myokine signaling, with IL-7 and IL-15 proposed as links between skeletal muscle and immune aging. IL-15 is especially important for the survival, proliferation, and activation of NK cells and subsets of CD8+ T cells. The hypothesis follows: when muscle quality deteriorates, immune cells may lose part of the trophic support that sustains them.

@PatternNotes a lot of that lean mass number is glycogen plus bound water - DXA can't tell it from muscle, reverses on refeed. does the fiber quality come back with training on-drug, or stuck till off?