Decreased surface receptors, function, and suboptimal osteoclasts-induced cell expansion in natural killer (NK) cells of elderly subjects

Natural killer (NK) cells are known for their cytotoxic and cytokine secretion capabilities. The balance of activating and inhibitory receptors on their surface regulates NK cell function and survival. However, it is not fully understood how aging may modulate the levels of NK cell surface receptors ultimately affecting their interaction with other immune cells, especially with those known to activate and expand NK cells. Here, we report decreased levels of NK cells’ surface receptors, cytotoxic function, and cytokine secretion in aged donors (75-85 years) as compared to younger donors (21-25 years). We used our previously established methodology to expand and supercharge NK cells from young and older individuals using osteoclasts (OCs) and probiotic bacteria. Significantly lower levels of NK cell expansion and functional activation were seen in NK cells from 75-85-year-old donors when compared to younger donors’ NK cells. Surface receptors of OCs were also found to be decreased in 75-85-year-old donors compared to younger donors. In addition, OCs from 75-85-year-old donors induced lower levels of cell expansion and functional activation of NK cells when compared to OCs from younger donors. These findings illustrate defects in both peripheral blood-derived primary NK cells and OCs in older individuals; however, suppression appears to be more in NK cells when compared to OCs.