The Aging Process: A Metabolomics Perspective

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Castro, Alex ; Signini, etore F. ; De Oliveira, Juliana Magalhaes ; Di Medeiros Leal, Maria Carolina Bezerra ; Rehder-Santos, Patricia ; Millan-Mattos, Juliana C. ; Minatel, Vinicius ; Pantoni, Camila B. F. ; Oliveira, Regina V. ; Catai, Aparecida M. ; Ferreira, Antonio G.

• Document type: Journal article
• Source: Molecules; v. 27, n. 24, p. 16-pg., 2022-12-01.

Abstract

Aging process is characterized by a progressive decline of several organic, physiological, and metabolic functions whose precise mechanism remains unclear. Metabolomics allows the identification of several metabolites and may contribute to clarifying the aging-regulated metabolic pathways. We aimed to investigate aging-related serum metabolic changes using a metabolomics approach. Fasting blood serum samples from 138 apparently healthy individuals (20-70 years old, 56% men) were analyzed by Proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS), and for clinical markers. Associations of the metabolic profile with age were explored via Correlations (r); Metabolite Set Enrichment Analysis; Multiple Linear Regression; and Aging Metabolism Breakpoint. The age increase was positively correlated (0.212 <= r <= 0.370, p < 0.05) with the clinical markers (total cholesterol, HDL, LDL, VLDL, triacylglyceride, and glucose levels); negatively correlated (-0.285 <= r <= -0.214, p < 0.05) with tryptophan, 3-hydroxyisobutyrate, asparagine, isoleucine, leucine, and valine levels, but positively (0.237 <= r <= 0.269, p < 0.05) with aspartate and ornithine levels. These metabolites resulted in three enriched pathways: valine, leucine, and isoleucine degradation, urea cycle, and ammonia recycling. Additionally, serum metabolic levels of 3-hydroxyisobutyrate, isoleucine, aspartate, and ornithine explained 27.3% of the age variation, with the aging metabolism breakpoint occurring after the third decade of life. These results indicate that the aging process is potentially associated with reduced serum branched-chain amino acid levels (especially after the third decade of life) and progressively increased levels of serum metabolites indicative of the urea cycle. (AU)

• FAPESP's process: 16/22215-7 - Impact of inspiratory muscle training and aging on metabolic mapping, autonomic modulation, and cardiovascular, respiratory and metabolic responses, and prediction of cardiorespiratory health through wearables
• Grantee: Aparecida Maria Catai
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/15040-4 - Omic-based strategies for the investigation of biomarkers for early diagnosis of patients with progressive biliary diseases
• Grantee: Juliana Magalhães de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/52070-4 - New approaches for evaluation of cardiovascular oscillations changes with aging
• Grantee: Aparecida Maria Catai
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/05965-8 - Metabolomic strategies based on LC-HRMS for investigation of potential biomarkers for clinical diagnosis - Phase I
• Grantee: Regina Vincenzi Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/13939-7 - Metabolomic analysis by Nuclear Magnetic Resonance (NMR) and mass spectrometry (LC-MS) of blood samples from individuals submitted to cardiorespiratory rehabilitation.
• Grantee: Alex Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/25082-3 - Study of the metabolic profile in active and sedentary aging: metabolomic approach
• Grantee: Étore de Favari Signini
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)