The past twenty years of work on an increasingly diverse set of aging clocks has comprehensively demonstrated that analysis of any sufficiently complex database of biological data will find correlations with age. Aging causes changes, driven by the accumulation of forms of cell and tissue damage. Since that damage is the same for everyone, even given individual variations in pace of aging there will be any number of specific age-related changes in biological data that run in much the same way in near all individuals. In an era in which obtaining and analyzing data costs little, we should expect to see a steady supply of papers such as the one noted here, in which researchers identify ever more specific age-related changes.
This study analyzed data from 51,904 UK Biobank participants to explore the association between 2,923 plasma proteins and nine aging-related phenotypes, including PhenoAge, KDM-Biological Age, healthspan, parental lifespan, frailty, and longevity. Protein levels were measured using proteomics. We utilized the DE-SWAN method to detect and measure the nonlinear alterations in plasma proteome during the process of biological aging. Mendelian randomization was applied to assess causal relationships, and a phenome-wide association study (PheWAS) explored the broader health impacts of these proteins.
We identified 227 proteins significantly associated with aging, with the pathway of inflammation and regeneration being notably implicated. Our findings revealed fluctuating patterns in the plasma proteome during biological aging in middle-aged adults, pinpointing specific peaks of biological age-related changes at 41, 60, and 67 years, alongside distinct age-related protein change patterns across various organs. Furthermore, Mendelian randomization further supported the causal association between plasma levels of CXCL13, DPY30, FURIN, IGFBP4, SHISA5, and aging, underscoring the significance of these drug targets. These five proteins have broad-ranging effects. The PheWAS analysis of proteins associated with aging highlighted their crucial roles in vital biological processes, particularly in overall mortality, health maintenance, and cardiovascular health. Moreover, proteins can serve as mediators in healthy lifestyle and aging processes.
Link: https://doi.org/10.1016/j.jare.2025.05.004
View the full article at FightAging
