Observed associations (A) and proposed mechanistic relationships (B) between adipose tissue, IL-15, natural killer (NK) cells, and muscle. (A) Positive associations are represented by green arrows. Inverse associations are represented by red arrows. All arrows are double-headed, indicating that associations do not necessarily imply mechanism. Mechanistic model (B) is based on our findings and on published literature. Stimulatory mechanisms are represented by green arrows and inhibitory mechanisms are represented by the red arrow. Double-headed green arrows indicate mutually positive stimulation. We propose that adipose tissue is a significant source of IL-15, especially in aging humans. IL-15 stimulates NK cells. Importantly, IL-15 forms part of a positive feedback loop between adipose tissue NK cells, other type 1 innate lymphocytes, and macrophages, as represented by the double-headed green arrows. IL-15 and other inflammatory agents weaken muscle.