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Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome.

Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), Lleida, Spain. Research Support Unit (USR) Lleida, Primary Care Services, Catalan Health Institute (ICS), Lleida, Spain. Fundació Institut Universitari per a la Recerca en Atenció Primària de Salut Jordi Gol i Gurina (IDIAP JGol), Lleida, Spain. Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. Department of Nursing, University of Girona, Girona, Spain. Department of Diabetes, Endocrinology and Nutrition, IDIBGI, Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain. Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, Spain. Department of Genetics, Physiology and Microbiology, Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Madrid, Spain. Department of Radiology (IDI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. Cardiovascular Genetics Center, CIBER-CV, IDIBGI, Girona, Spain. Vascular Health Research Group of Girona (ISV-Girona), Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Girona, Spain. Primary Care Services, Catalan Institute of Health (ICS), Girona, Spain. Department of Neurology, Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain. Department of Computer Science, Applied Mathematics and Statistics, University of Girona, Girona, Spain. Institut Investigació Germans Trias i Pujol (IGTP), Comparative Medicine and Bioimage of Catalonia, Barcelona, Spain.

Aging cell. 2023;(6):e13821
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Abstract

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial β-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.