Centenarians represent a unique demographic characterized by exceptional longevity and a delayed onset of age-related diseases, making them an invaluable population for identifying proteins linked to successful aging. While the mechanisms underlying such remarkable healthspan remain largely unexplored, the discovery of complementary biomarkers could offer significant insights into healthy aging processes and potential therapeutic targets. Without a priori knowledge of specific protein targets, we utilized proteomics to investigate the immune and cardiometabolic protein expression (PEA, Olink) profiles in the plasma of centenarians. This proteomic approach allowed us to generate hypothesis-free models.
Our research identified a robust set of aging-associated proteins (APs) that are most predictive of successful aging and longevity, which can be used for target discovery and downstream analysis in the field of precision medicine for healthy aging. We characterized plasma protein profiles from centenarians within the SWISS100 cohort and compared them to hospitalized geriatric patients (age 80-90 years) and younger healthy participants (age 30-60 years). Key findings were further validated by:
Replicating associations of 23 proteins with a standard set of APs developed by the Targeting Aging with Metformin (TAME) consortium.
Identifying 135 differentially expressed proteins (DEPs) with consistent aging directions through comparison with an independent centenarian proteomics study (New England Centenarian Study, NECS).
Furthermore, applying fractional polynomial regressions, we uncovered proteins with linear and non-linear age-associated profiles and identified a subgroup of 37 proteins exhibiting a "younger" signature in centenarians. Pathway enrichment analyses of these 37 proteins highlighted critical processes such as programmed cell death, metabolic enzyme pathways, regulation of extracellular matrix stability, immune and inflammatory responses, and neurotrophic signaling pathways.
SWISS100 website: https://wp.unil.ch/swiss100/
- Article: Delhaes, F., Falciola, J., Hoffman, A., Carnesecchi, S., Cavalli, S., von Gunten, A., Jopp, D. S., Herrmann, F. R., & Krause, K.-H. (2026). Plasma proteome profiling of centenarian across Switzerland reveals key youth-associated proteins. Aging Cell. https://doi.org/10.1111/acel.70409
- Dataset: Delhaes, F. (2026). SWISS100_PROTEOMICS_NPX_Data. Zenodo. https://doi.org/10.5281/zenodo.18403090