김연희 (충남대학교 생명정보융합학과)

김현수 (충남대학교 생명과학과/생명정보융합학과)

김연희 (충남대학교 생명정보융합학과)

지재호 (충남대학교 단백질시스템연구실)

김현수 (충남대학교 생명과학과/생명정보융합학과)

Aging involves progressive physiological deterioration, yet underlying molecular mechanisms remain poorly understood. While age-related protein expression changes are well-documented, functional aging consequences are equally influenced by alterations in protein conformation and protein-protein interaction (PPI) networks. We present a comprehensive analysis of age-dependent structural dynamics in plasma proteins, integrating experimental proteomics with computational structural biology. Using covalent protein painting (CPP) labeling coupled with multiple reaction monitoring LC-MS/MS, we assessed conformational changes across four age groups (20s-50s) in 24 healthy individuals (n=6 per decade). Through cosine similarity analysis and limma-based statistical modeling, we identified five distinct age-associated conformational patterns, from progressive structural opening to closure, encompassing 27 proteins and 57 peptides. Network analysis revealed coordinated structural remodeling among key protein interactors, suggesting synchronized conformational changes within functional complexes. We verified specific conformational change sites using AlphaFold3 Multimer, mapping precise regions undergoing age-related remodeling within protein complexes. These findings illuminate the dynamic aging plasma proteome and establish a framework for identifying conformational biomarkers of healthy aging and age-related disease susceptibility.