Serum soluble mediator waves and networks along healthy ageing.

Abstract

The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3Yrs to >70Yrs). A broad increase in serum soluble mediators was observed at 6-10Yrs with subsequent decline at 11-20Yrs and 21-30Yrs followed by a second round of upregulation starting at 31-40Yrs, with a large increase at 51-60Yrs and a marked decline at age >70Yrs. Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6-10Yrs and a second wave around 61-70Yrs. A universal decline was observed later at age >70Yrs. In males, the second wave started earlier at 31-40Yrs with a peak at 51-60Yrs and a further smooth decline towards >70Yrs. Conversely, in females, the first peak extended from 3-5Yrs to 6-10Yrs and the second wave starting around 41-50Yrs with a peak at 61-70Yrs followed by a sharp decline at >70Yrs. Overall, CCL11, CXCL8, IL-1β, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31-40Yrs) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3-5Yrs, with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11-20Yrs, 51-60Yrs and >70Yrs) than in males (at 21-30Yrs, 61-70Yrs). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes.