Aging is characterized by declines in physiological function that increase risk of age-associated diseases and limit healthspan, mediated in part by chronic low-grade inflammation. Interleukin (IL)-37 suppresses inflammation in pathophysiological states but has not been studied in the context of aging in otherwise healthy humans. Thus, we investigated associations between IL-37 and markers of healthspan in 271 young (18–39 years; n = 41), middle-aged (40–64 years; n = 162), and older (65 + years; n = 68) adults free of overt clinical disease. After conducting a thorough validation of AdipoGen’s IL-37 ELISA, we found that plasma IL-37 is lower in older adults (young: 339 ± 240, middle-aged: 345 ± 234; older: 258 ± 175 pg/mL; P = 0.048), despite elevations in pro-inflammatory markers. As such, the ratios of circulating IL-37 to pro-inflammatory markers were considerably lower in older adults (e.g., IL-37 to C-reactive protein: young, 888 ± 918 vs. older, 337 ± 293; P = 0.02), indicating impaired IL-37 responsiveness to a pro-inflammatory state with aging and consistent with the notion of immunosenescence. These ratios were related to multiple indicators of healthspan, including positively to cardiorespiratory fitness (P < 0.01) and negatively to markers of adiposity, blood pressure, and blood glucose (all P < 0.05). Lastly, we correlated single-nucleotide polymorphisms (SNPs) in the IL37 and ILR8 (the co-receptor for IL-37) genes and found that variants in IL37 SNPs tended to be associated with blood pressure and adiposity (P = 0.08–0.09) but did not explain inter-individual variability in circulating IL-37 concentrations across age (P ≥ 0.23). Overall, our findings provide novel insights into a possible role of IL-37 in biological aging in humans.

衰老的特点是生理功能下降，从而增加与年龄相关的疾病的风险并限制健康寿命，这在一定程度上是由慢性低度炎症介导的。白细胞介素 (IL)-37 可抑制病理生理状态下的炎症，但尚未在其他健康人类的衰老背景下进行研究。 因此，我们调查了 271 名年轻人（ 18-39 岁； n  = 41）、中年人（40-64 岁；n  = 162）和老年人（65 岁以上；n = 162 ）中 IL-37 与健康寿命标志物之间的关联。68) 没有明显临床疾病的成年人。对 AdipoGen 的 IL-37 ELISA 进行彻底验证后，我们发现老年人的血浆 IL-37 较低（年轻：339 ± 240，中年：345 ± 234；老年：258 ± 175 pg/mL；P  = 0.048），尽管促炎标记物有所升高。因此，老年人中循环 IL-37 与促炎标志物的比率相当低（例如，IL-37 与 C 反应蛋白：年轻人，888 ± 918 vs 老年人，337 ± 293；P = 0.02  ） ，表明随着年龄的增长，IL-37 对促炎状态的反应能力受损，这与免疫衰老的概念一致。这些比率与健康寿命的多个指标相关，包括与心肺健康呈正相关（P  < 0.01），与肥胖、血压和血糖指标呈负相关（均P  < 0.05）。最后，我们对IL37和ILR8（IL-37 的共同受体）基因中的单核苷酸多态性 (SNP) 进行了关联，发现IL37 SNP 的变异往往与血压和肥胖相关（P  = 0.08–0.09）但没有解释循环IL-37浓度随年龄变化的个体间差异（P≥0.23  ）。总的来说，我们的研究结果为 IL-37 在人类生物衰老中可能发挥的作用提供了新的见解。