Long-term temporal stability of circulating proteins in older adults

Circulating proteins provide insights into an individual's health and aging trajectory. However, little is known about their long-term temporal stability. We evaluated the five-year temporal stability of 7288 serum proteins in 3093 participants (mean age 75 years) of the AGES-Reykjavik study. We observe wide variability in protein temporal stability, independent of transcriptomic stability in tissues. Temporally stable proteins tend to be extracellular, secreted, and tissue-specific, while temporally variable proteins are typically involved in intracellular housekeeping functions. Generally, protein levels become more stable with age, and for some proteins, temporal stability differs by sex. Similar patterns and consistent temporal stability were observed for a subset of plasma proteins in the Cardiovascular Health Study. Genetic factors and disease state have widespread effects on the temporal stability of the proteome, while the co-regulatory structure of the proteome is largely retained over time. Our findings underscore the protein-specific differences in long-term temporal stability, which are particularly important to consider in the context of biomarker development and precision medicine.