{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T01:48:23Z","timestamp":1775180903816,"version":"3.50.1"},"reference-count":0,"publisher":"Aging and Disease","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["aging dis"],"abstract":"<jats:p>Biological aging is a major determinant of frailty, functional decline, and vulnerability to age-related diseases; however, its upstream metabolic and inflammatory signatures remain incompletely understood. We investigated biological aging using an integrated multi-omics approach in a clinically enriched human cohort. In this prospective study, 120 patients with adult spinal deformity (ASD) and 480 age- and sex-matched healthy controls were included for comparison of PhenoAge. Within the ASD cohort, high-resolution plasma metabolomics and targeted proteomics were performed to characterize metabolic and inflammatory correlates of biological aging. A composite trimethylamine N-oxide (TMAO) Pathway Index (TPI) was constructed using standardized methylamine-related metabolites. Biological age was significantly elevated in ASD compared with matched controls. Within the ASD cohort, metabolomic profiling revealed enrichment of methylamine-related and glycation-associated metabolites among the strongest correlations of PhenoAge. The TPI showed a strong, age-independent, near-linear association with PhenoAge. In sensitivity analyses adjusted for age, sex, BMI, smoking status, and eGFR, this association remained significant (\u03b2 = 2.92, 95% CI 0.74-5.10, p = 0.009). Targeted proteomic analyses showed that tumor necrosis factor-\u03b1 was selectively associated with both PhenoAge and the TPI, whereas associations with interleukin-1\u03b2, interleukin-6, and adiponectin were limited. Higher PhenoAge was also associated with reduced physical performance, increased frailty, and impaired health-related quality of life. These findings support an exploratory, hypothesis-generating framework in which methylamine-related metabolism and chronic inflammatory signaling are associated with biological aging in ASD. Because of the cross-sectional design, these results should be interpreted as associative rather than causal.<\/jats:p>","DOI":"10.14336\/ad.2026.0237","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T01:04:52Z","timestamp":1775178292000},"source":"Crossref","is-referenced-by-count":0,"title":["Microbiome-Linked Metabolic Architecture of Accelerated Biological Aging in Humans"],"prefix":"10.14336","member":"5462","published-online":{"date-parts":[[2026]]},"container-title":["aging and disease"],"original-title":[],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T01:04:53Z","timestamp":1775178293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2026.0237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14336\/ad.2026.0237","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}