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Article

The Aging Process: A Metabolomics Perspective

by
Alex Castro
1,*,
Étore F. Signini
2,
Juliana Magalhães De Oliveira
1,
Maria Carolina Bezerra Di Medeiros Leal
1,
Patrícia Rehder-Santos
2,
Juliana C. Millan-Mattos
2,
Vinicius Minatel
2,
Camila B. F. Pantoni
2,
Regina V. Oliveira
1,
Aparecida M. Catai
2 and
Antônio G. Ferreira
1,*
1
Department of Chemistry, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil
2
Department of Physiotherapy, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil
*
Authors to whom correspondence should be addressed.
Molecules 2022, 27(24), 8656; https://doi.org/10.3390/molecules27248656
Submission received: 28 September 2022 / Revised: 29 October 2022 / Accepted: 2 December 2022 / Published: 7 December 2022
(This article belongs to the Special Issue Applications and Method Developments in NMR – from Benchtop to High Field NMR Spectroscopy)
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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.
Keywords: metabolism; metabolome; nuclear magnetic resonance; liquid chromatography-high-resolution mass spectrometry metabolism; metabolome; nuclear magnetic resonance; liquid chromatography-high-resolution mass spectrometry

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MDPI and ACS Style

Castro, A.; Signini, É.F.; De Oliveira, J.M.; Di Medeiros Leal, M.C.B.; Rehder-Santos, P.; Millan-Mattos, J.C.; Minatel, V.; Pantoni, C.B.F.; Oliveira, R.V.; Catai, A.M.; et al. The Aging Process: A Metabolomics Perspective. Molecules 2022, 27, 8656. https://doi.org/10.3390/molecules27248656

AMA Style

Castro A, Signini ÉF, De Oliveira JM, Di Medeiros Leal MCB, Rehder-Santos P, Millan-Mattos JC, Minatel V, Pantoni CBF, Oliveira RV, Catai AM, et al. The Aging Process: A Metabolomics Perspective. Molecules. 2022; 27(24):8656. https://doi.org/10.3390/molecules27248656

Chicago/Turabian Style

Castro, Alex, Étore F. Signini, Juliana Magalhães De Oliveira, Maria Carolina Bezerra Di Medeiros Leal, Patrícia Rehder-Santos, Juliana C. Millan-Mattos, Vinicius Minatel, Camila B. F. Pantoni, Regina V. Oliveira, Aparecida M. Catai, and et al. 2022. "The Aging Process: A Metabolomics Perspective" Molecules 27, no. 24: 8656. https://doi.org/10.3390/molecules27248656

APA Style

Castro, A., Signini, É. F., De Oliveira, J. M., Di Medeiros Leal, M. C. B., Rehder-Santos, P., Millan-Mattos, J. C., Minatel, V., Pantoni, C. B. F., Oliveira, R. V., Catai, A. M., & Ferreira, A. G. (2022). The Aging Process: A Metabolomics Perspective. Molecules, 27(24), 8656. https://doi.org/10.3390/molecules27248656

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