Research Paper Volume 13, Issue 4 pp 4850—4880

Metabolic footprint of aging and obesity in red blood cells

Inés Domingo-Ortí1, , Rubén Lamas-Domingo2, , Andreea Ciudin3,4, , Cristina Hernández3,4, , José Raúl Herance5,6, , Martina Palomino-Schätzlein2, , Antonio Pineda-Lucena1,7, ,

  • 1 Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026, Spain
  • 2 NMR Facility, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain
  • 3 Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, Barcelona 08035, Spain
  • 4 CIBERDEM (Instituto de Salud Carlos III), Madrid 28029, Spain
  • 5 Medical Molecular Imaging Research Group, Vall d’Hebron Research Institute, CIBBIM-Nanomedicine, Barcelona 08035, Spain
  • 6 CIBERBBN (Instituto de Salud Carlos III), Madrid 28029, Spain
  • 7 Medicinal Chemistry Laboratory, Centro de Investigación Médica Aplicada, Pamplona 31008, Spain

Received: October 28, 2020       Accepted: February 8, 2021       Published: February 19, 2021
How to Cite

Copyright: © 2021 Domingo-Ortí et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aging is a physiological process whose underlying mechanisms are still largely unknown. The study of the biochemical transformations associated with aging is crucial for understanding this process and could translate into an improvement of the quality of life of the aging population. Red blood cells (RBCs) are the most abundant cells in humans and are involved in essential functions that could undergo different alterations with age. The present study analyzed the metabolic alterations experienced by RBCs during aging, as well as the influence of obesity and gender in this process. To this end, the metabolic profile of 83 samples from healthy and obese patients was obtained by Nuclear Magnetic Resonance spectroscopy. Multivariate statistical analysis revealed differences between Age-1 (≤45) and Age-2 (>45) subgroups, as well as between BMI-1 (<30) and BMI-2 (≥30) subgroups, while no differences were associated with gender. A general decrease in the levels of amino acids was detected with age, in addition to metabolic alterations of glycolysis, the pentose phosphate pathway, nucleotide metabolism, glutathione metabolism and the Luebering-Rapoport shunt. Obesity also had an impact on the metabolomics profile of RBCs; sometimes mimicking the alterations induced by aging, while, in other cases, its influence was the opposite, suggesting these changes could counteract the adaptation of the organism to senescence.


1H-NMR: Proton nuclear magnetic resonance; AMP: Adenosine monophosphate; ATP: Adenosine triphosphate; BCAAs: Branched-chain amino acids; BMI: Body mass index; BMRB: Biological Magnetic Resonance Bank; FID: Free induction decay; HbA1c: Glycated haemoglobin; HDL: High density lipoprotein; HMDB: Human metabolome database; HSQC: Heteronuclear single quantum correlation; IMP: Inosine monophosphate; LDL: Low density lipoprotein; NAD+: Nicotinamide adenine dinucleotide; NADP+: Nicotinamide adenine dinucleotide phosphate; OPLS-DA: Orthogonal projections to latent structures discriminant analysis; PCA: Principal component analysis; PLS: Projection on latent structure; PPP: Pentose phosphate pathway; PRPP: Phosphoribosyl pyrophosphate; TG: Triglycerides; TOCSY: Total correlation spectroscopy; TSP: Trimethylsilylpropanoic acid; VIP: Variable importance in projection.

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