Circulating interleukin-37 declines with aging in healthy humans: relations to healthspan indicators and IL37 gene SNPs.

Autor: Brunt VE; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA. vienna.brunt@cuanschutz.edu.; Department of Medicine, University of Colorado Denver Anschutz Medical Campus, CO, 80045, Aurora, USA. vienna.brunt@cuanschutz.edu., Ikoba AP; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA., Ziemba BP; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA., Ballak DB; 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., Hoischen A; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Human Genetics & Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Dinarello CA; Department of Medicine, University of Colorado Denver Anschutz Medical Campus, CO, 80045, Aurora, USA.; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Ehringer MA; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA., Seals DR; Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2023 Feb; Vol. 45 (1), pp. 65-84. Date of Electronic Publication: 2022 May 27.
DOI: 10.1007/s11357-022-00587-3
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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