Research Paper Advance Articles

Plasma acylcarnitine levels increase with healthy aging

Zachery R. Jarrell1, , M. Ryan Smith1, , Xin Hu1, , Michael Orr1, , Ken H. Liu1, , Arshed A. Quyyumi2, , Dean P. Jones1, , Young-Mi Go1, ,

  • 1 Division of Pulmonary, Allergy and Critical Care Medicine, Atlanta, GA 30322, USA
  • 2 Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA

Received: February 21, 2020       Accepted: May 27, 2020       Published: June 16, 2020      

https://doi.org/10.18632/aging.103462
How to Cite

Copyright © 2020 Jarrell 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.

Abstract

Acylcarnitines transport fatty acids into mitochondria and are essential for β-oxidation and energy metabolism. Decreased mitochondrial activity results in increased plasma acylcarnitines, and increased acylcarnitines activate proinflammatory signaling and associate with age-related disease. Changes in acylcarnitines associated with healthy aging, however, are not well characterized. In the present study, we examined the associations of plasma acylcarnitines with age (range: 20-90) in 163 healthy, non-diseased individuals from the predictive medicine research cohort (NCT00336570) and tested for gender-specific differences. The results show that long-chain and very long-chain acylcarnitines increased with age, while many odd-chain acylcarnitines decreased with age. Gender-specific differences were observed for several acylcarnitines, e.g., eicosadienoylcarnitine varied with age in males, and hydroxystearoylcarnitine varied in females. Metabolome-wide association study (MWAS) of age-associated acylcarnitines with all untargeted metabolic features showed little overlap between genders. These results show that plasma concentrations of acylcarnitines vary with age and gender in individuals selected for criteria of health. Whether these variations reflect mitochondrial dysfunction with aging, mitochondrial reprogramming in response to chronic environmental exposures, early pre-disease change, or an adaptive response to healthy aging, is unclear. The results highlight a potential utility for untargeted metabolomics research to elucidate gender-specific mechanisms of aging and age-related disease.

Abbreviations

AE: anion exchange; BCAA: branched-chain amino acid; CoA: coenzyme A; FDR: false discovery rate; HCA: hierarchical clustering analysis; HRM: high resolution metabolomics; LC: long-chain; MC: medium-chain; MWAS: metabolome-wide association study; m/z: mass-to-charge ratio; OC: odd-chain; RT: retention time; SLC: Schymanski level of confidence; SC: short-chain; VLC: very long-chain.