Meta-Analysis and Bioinformatic Analysis of Human Fluid Proteomic Studies Reveal Key Biological Pathways Related to Aging and Frailty

Aging research seeks to understand the progressive decline in physiological function throughout adulthood. Frailty is a significant clinical manifestation of aging. Recent discoveries of global telomere(definition) attrition, cellular senescence(definition))." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">hallmarks of aging(definition) have paved the way for deeper insight into its molecular mechanisms. Proteomics has emerged as a powerful approach, given the proteome's sensitivity to environmental changes. This study aimed to uncover novel biological insights into aging by analyzing proteins that are significantly associated with chronological age or frailty. We conducted a systematic review of Medline and Embase up to August 2024 to find studies involving adults that used proteomic analyses. From each study, we compiled the significant proteins consistently reported across age-related or frailty-related studies by extracting statistical outcomes and expression patterns. Significant proteins were compared, and pathway enrichment analysis was performed using STRING software. Our analysis included 2,630 age-associated proteins from 27 studies and 194 frailty-associated proteins from 8 studies. We identified 177 shared proteins for both age and frailty, including nine with opposite expression trends. Meta-regression and pathway analyses revealed convergence on key biological processes, including immunity, inflammation, metabolism, homeostasis, coagulation, and neurology. These findings suggest that age- and frailty-related proteomic studies provide complementary insights into understanding the overall complexity of the biology of aging. This integrative approach emphasizes the potential of proteomics not only for biomarker discovery but also for advancing our understanding of our functional capacities. Future multi-omics studies will be essential for further elucidating the complex molecular landscape of aging.