Metabolic Profiling Reveals Organ-Specific Molecular Pathologies and Aging-Associated Biomarkers in Progeroid Laminopathy

Abstract

The molecular mechanisms linking premature and physiological aging remain incompletely understood. Here, we present a cross-species, multi-organ metabolic atlas of progeroid laminopathy (PL) generated through integrated lipidomic and metabolomic profiling of heart, lung, skin, and serum from Hutchinson–Gilford progeria syndrome (HGPS) mouse models and human PL cohorts. We identify organ-specific metabolic alterations, with the most pronounced changes observed in the skin at the omics level. Notably, we uncover disruption of a taurine–TCA–TUDCA cytoprotective axis, suggesting a coordinated metabolic vulnerability in PL. Serum profiling further reveals candidate circulating biomarkers, including increased LPC(18:1e) and LysoPA along with decreased D-glucose 1-phosphate and NAD. These alterations are conserved across species and, importantly, display concordant trends in independent cohorts of physiologically aged healthy individuals. This overlap indicates a partial convergence between PL-associated and normal aging-related metabolic changes. Together, our findings provide a metabolic framework for understanding PL pathophysiology and highlight clinically accessible biomarkers that warrant future longitudinal validation.

Keywords

aging / biomarker discovery / Hutchinson–Gilford progeria syndrome / multi-omics / progeroid laminopathy

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