Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Department of Medicine, University of Colorado Denver Anschutz Medical Campus, CO, 80045, Aurora, USA.
Geroscience. 2023 Feb;45(1):65-84. doi: 10.1007/s11357-022-00587-3. Epub 2022 May 27.
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.
衰老是生理功能下降的特征，增加了与年龄相关疾病的风险，并限制了健康寿命，部分原因是慢性低度炎症。白细胞介素 (IL)-37 抑制病理生理状态下的炎症，但在其他方面健康的老年人中尚未在衰老背景下进行研究。因此，我们在 271 名年轻（18-39 岁；n=41）、中年（40-64 岁；n=162）和老年（65+岁；n=68）成年人中研究了 IL-37 与健康寿命标志物之间的关联，这些成年人没有明显的临床疾病。在对 AdipoGen 的 IL-37 ELISA 进行彻底验证后，我们发现老年组的血浆 IL-37 水平较低（年轻组：339±240，中年组：345±234；老年组：258±175 pg/mL；P=0.048），尽管促炎标志物升高。因此，老年组循环 IL-37 与促炎标志物的比值明显较低（例如，IL-37 与 C 反应蛋白：年轻组为 888±918，老年组为 337±293；P=0.02），表明随着年龄的增长，IL-37 对促炎状态的反应受损，这与免疫衰老的概念一致。这些比值与健康寿命的多个指标相关，包括与心肺适能呈正相关（P<0.01），与肥胖、血压和血糖标志物呈负相关（均 P<0.05）。最后，我们还对 IL37 和 ILR8（IL-37 的共受体）基因中的单核苷酸多态性（SNP）进行了相关性分析，发现 IL37 SNP 中的变体往往与血压和肥胖有关（P=0.08-0.09），但不能解释 IL-37 浓度在整个年龄范围内的个体间变异性（P≥0.23）。总的来说，我们的发现为 IL-37 在人类生物学衰老中的可能作用提供了新的见解。
