Plasma proteins link metabolomic aging to disease and mortality in humans
Researchers analyzed UK Biobank data to identify causal circulating proteins that correlate with a refined metabolomic aging clock.
In a preprint analyzing 400,594 human participants from the UK Biobank, researchers mapped the circulating protein profile associated with metabolomic aging. The team created MetScore2 using 325 nuclear magnetic resonance biomarkers. Higher MetScore2 values marked earlier onset of age-related diseases, and faster score increases predicted higher mortality. A proteome-wide association study showed that associated plasma protein signatures were broadly similar in both sexes and fluctuated across mid-to-late adulthood, with peaks at ages 50, 57, and 65. Integrating genetic analyses, Mendelian randomization, and colocalization revealed IL1RN, ARG1, NCAN, F11R, SERPINF2, and NBL1 as putative causal proteins with distinct disease associations.
Why it matters
Mapping the proteomic architecture of metabolomic aging helps pinpoint specific circulating factors that may drive biological aging and age-related disease.
Caveats
The study is a preprint that has not yet undergone peer review. In addition, the identified causal candidates rely on statistical genetic methods in a single cohort and require functional validation.
The paper
Metabolomic profiling identifies plasma protein biomarkers of biological aging
Luo X, Liu C, Xie Y et al.
medRxiv · 28 Sep 2026 · Preprint, not yet peer-reviewed