Proteomic Signatures Over Age Reveal Significant Changes From Infancy Till Late Adulthood

Biomarkers are essential in drug development and diagnostics, aiding patient selection and disease monitoring. The lack of age‐specific protein references complicates tracking patterns related to chronic disease or treatment. This exploratory, proof‐of‐concept study explores age‐related changes in the serum proteome across the full human lifespan. Using proximity extension assays (Olink), we measured the Immuno‐oncology panel in serum from 264 healthy individuals, another panel in a subgroup of 109, all without significant disease at blood draw, aged 0 days to 88 years. Cluster analysis of the Immuno‐oncology panel revealed two clusters: cluster 1 included samples from children ≤11 days, cluster 2 encompassing samples with an age range from 2 months till 88 years old. Weighted correlation network analysis identified five protein modules, with four showing enrichment in specific pathways. The Organ‐Damage panel showed similar age‐related protein variations. Finally, we identified four protein patterns over age: constant, increasing, decreasing, or U‐shaped and defined age‐specific normal expression ranges. Altogether, our findings suggest that healthy aging across the entire lifespan involves alterations in protein expressions and distinct protein profiles exist in newborns, children, adults and older adults. We provide valuable reference data for the different protein patterns observed across the entire lifespan.