RT Journal Article SR Electronic T1 Metabolomic profiling revels systemic signatures of premature aging induced by Hutchinson-Gilford Progeria Syndrome JF bioRxiv FD Cold Spring Harbor Laboratory SP 554220 DO 10.1101/554220 A1 Gustavo Monnerat A1 Geisa Paulino Caprini Evaristo A1 Joseph Albert Medeiros Evaristo A1 Caleb Guedes Miranda dos Santos A1 Gabriel Carneiro A1 Leonardo Maciel A1 Vânia Oliveira Carvalho A1 Fábio César Sousa Nogueira A1 Gilberto Barbosa Domont A1 Antonio Carlos Campos de Carvalho YR 2019 UL http://biorxiv.org/content/early/2019/02/19/554220.abstract AB Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder. HGPS children present a high incidence of cardiovascular complications along with altered metabolic processes and accelerated aging process. No metabolic biomarker is known and the mechanisms underlying premature aging are not fully understood. The present study analysed plasma from six HGPS patients of both sexes (7.7±1.4 years old; mean±SD) and eight controls (8.6±2.3 years old) by LC-MS/MS in high-resolution non-targeted metabolomics (Q-Exactive Plus). Several endogenous metabolites with statistical difference were found. Multivariate statistics analysis showed a clear separation between groups. Potential novel metabolic biomarkers are identified using the multivariate area under ROC curve (AUROC) based analysis, showing an AUC value higher than 0.80 using only two metabolites, and reaching 1.00 when increasing the number of metabolites in the AUROC model. Targeted metabolomics was used to validate some of the metabolites identified by the non-targeted method. Taken together, changed metabolic pathways in that panel involve sphingolipid, amino acid, and oxidation of fatty acids among others. In conclusion our data show significant alterations in cellular energy use and availability, in signal transduction, and in lipid metabolites, creating new insights on metabolic alterations associated with premature aging.