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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\u2010aged 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\u2010aged 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\u2010aged mice. NK cell function was significantly reduced in the spleen, bone marrow, and adipose tissues of these middle\u2010aged mice. Young mice with diet\u2010induced 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.<\/jats:p>","DOI":"10.1111\/acel.70707","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:04:56Z","timestamp":1789455896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Killer Cell Dysfunction Is Emerging During Midlife Obesity"],"prefix":"10.1111","volume":"25","author":[{"given":"Ruojia","family":"Biao","sequence":"first","affiliation":[{"name":"Peking University Ditan Teaching Hospital  Beijing China"},{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital Capital Medical University  Beijing China"},{"name":"Beijing Institute of Infectious Diseases  Beijing China"},{"name":"National Center for Infectious Diseases, 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