Natural Killer Cell Dysfunction Is Emerging During Midlife Obesity

Individuals in the middle-aged demographic are notably more vulnerable to obesity, facing a higher risk of mortality from all causes. However, it remains unclear whether the reduction in life expectancy is related to dysregulated natural killer (NK) cell function triggered by the microenvironment of adiposity in middle age. In the present study, we observed that healthy middle-aged donors and mice displayed compromised NK cell function compared to their younger counterparts, particularly in males. The quantity and maturation of NK cells were significantly diminished in both spleen and white adipose tissues (WATs), coinciding with an increase in WAT volume and a reduced basal metabolic rate in middle-aged mice. We further established that heightened apoptosis coupled with a reduction in cell proliferation might contribute to the diminished NK cell counts in the spleens of middle-aged mice. NK cell function was significantly reduced in the spleen, bone marrow, and adipose tissues of these middle-aged mice. Young mice with diet-induced obesity also exhibited impaired NK cell function. In summary, our findings indicate a reduction in both the quantity and functional efficacy of NK cells, which is associated with the rising prevalence of obesity during middle age.