Matched Plasma and Tissue Proteomics Reveal the Selective Nature of Circulating Biomarkers of Human Aging
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Aging is systemic, yet how circulating proteins reflect molecular aging within solid tissues remains unclear. We profiled 5,415 proteins using Olink Explore HT in 178 adults aged 20-87 years, including matched plasma-muscle (n = 56) and plasma-ovary (n = 24) pairs. Plasma-tissue concordance was limited, with 50 muscle and 17 ovarian proteins significantly correlated, indicating that plasma selectively reflects tissue protein abundance. Age-correlated proteins and pathways differed markedly across sex and tissue strata, Including immune/inflammatory signatures in female plasma, vascular and extracellular-matrix pathways in male plasma, and collagen remodeling in the ovary. Expression Variation Analysis further revealed predominantly context-specific age-related changes in protein coordination, including FAS/FADD/TRAIL death-receptor networks in plasma and a TP53-CDKN1A senescence-associated axis in muscle. Exploratory multivariate models identified additional plasma associations with subsets of tissue proteins, including tissue-restricted muscle proteins. Together, these findings define plasma as a selective, context-dependent window into human tissue aging.
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
Award: G2522469244
OpenAlex ID: W7223468005