Review Volume 4, Issue 8 pp 535—546

Figure 1. Proposed model of skeletal muscle, adipose tissue, and NK cells in aging.

Muscle negatively regulates adipose tissue via IL-15 and possibly other myokines. In turn, inflammatory adipokines produced by adipose tissue, especially visceral fat, negatively regulate muscle. These same myokines and adipokines are proposed to affect NK cells. IL-15 is required for NK cell development and survival, whereas inflammatory cytokines such as TNF-α and IL-6 shorten NK cell survival or stimulate NK cells to produce pro-inflammatory IL-17. During aging, muscle mass, strength, and endurance decline, which we propose results in less IL-15 production. At the same time, increased adipose tissue that is characteristic of aging is associated with increased inflammatory adipokine production. We propose that these changing myokines and adipokine levels negatively affect NK cells during aging.