Circulating lipocalin-2 across the adult lifespan

Lipocalin-2 (LCN2), a hormone produced by adipocytes, osteoblasts, and renal tubular cells, is implicated in age-related diseases, including cardio-metabolic disease. To understand the role LCN2 may play in pathological states, we first need to elucidate the relationship between circulating LCN2 with indices of cardio-metabolic health during "normal" aging. This study examined the relationship between serum levels of LCN2, age, and cardio-metabolic measures across the adult lifespan in males and females. We conducted a pooled cohort analysis including 124 community-dwelling males (<i>n</i> = 52) and females (<i>n</i> = 72) (age 20-87 yr, median BMI 25.92 [23.04, 29.81] kg/m²). Serum LCN2 was analyzed using a two-step chemiluminescent microparticle monoclonal immunoassay. The relationship between LCN2 and age was evaluated by linear regression and cubic spline. Simple linear regressions were performed to investigate the relationship between LCN2 and the following variables: BMI, VO_2peak, serum glucose, and body composition (DXA). For every 1 yr increase in age, LCN2 levels were 0.26 mg/L higher (<i>P</i> = .007, 95% CI [0.07, 0.45]). Each 1 unit increase in BMI (kg/m²) was associated with 0.88 mg/L higher LCN2 levels (<i>P</i> = .027, [0.10, 1.66]) and each 1 unit increase in VO_2peak (mL/kg/min) was associated with 0.38 mg/L lower LCN2 (<i>p</i> = .003, [-0.63, -0.13]).There was no significant relationship between LCN2 and sex, glucose levels or body composition (all <i>p</i> > .05). LCN2 increased linearly across the adult lifespan while it decreased as fitness level increased. Future research should build on these findings to determine whether LCN2 can be used as a biomarker for chronic disease and if exercise can mitigate age-related disease associated with LCN2 changes.