Beyond chronological age: Sex and IL-6 are associated with natural killer cell and monocyte counts in a Sicilian cohort spanning adulthood to extreme longevity

Aims: This study aimed to characterise the natural killer (NK; CD3-CD16+CD56+) and monocyte compartments in 54 participants by analysing absolute cell counts in relation to age, sex, cytomegalovirus (CMV) serostatus, an established marker of immune ageing, and interleukin-6 (IL-6) values, as an indicator of inflamm-ageing. Methods: The analysis was conducted in a cohort of Sicilians (28 females and 26 males) aged 19-110 years, including 20 adults (19-64 years), 15 older adults (68-88 years), 11 long-living individuals (93-104 years), and 8 semi- and supercentenarians (105-110 years; hereafter referred to as the oldest centenarians). Multiple negative binomial regression models were used to assess the independent effects of age, sex, CMV serostatus, and IL-6 concentrations on NK and monocyte counts. Results: Although NK cells and monocytes are generally reported to increase with age, adjustment for covariates revealed that NK cell counts showed only a non-significant age-related trend. In contrast, no statistically significant independent association with age was detected for monocytes. A statistically significant sex effect emerged, with men exhibiting higher NK cell counts than women. Monocyte counts were significantly and positively associated with IL-6 levels. Conclusion: These findings suggest that previously reported associations of advanced age, particularly extreme longevity, with higher NK-cell and monocyte counts may not be independent of sex, in the case of NK cells, or of chronic low-grade inflammation, as reflected by IL-6 levels, in the case of monocytes. Given the observational design, these results should be interpreted as adjusted associations rather than evidence of mediation or causality.