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Research Paper|Volume 11, Issue 1|pp 73—88

Elevated plasma ceramide levels in post-menopausal women: a cross-sectional study

Valentina Vozella1, Abdul Basit1, Fabrizio Piras2, Natalia Realini1, Andrea Armirotti1, Paola Bossù3, Francesca Assogna2, Stefano L. Sensi4,5,6, Gianfranco Spalletta2,7, Daniele Piomelli8
  • 1Department of Drug Discovery and Development, Italian Institute of Technology, Genova 16163, Italy
  • 2Department of Clinical and Behavioral Neurology, Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome 00179, Italy
  • 3Department of Clinical and Behavioral Neurology, Laboratory of Experimental Neuropsychobiology, IRCCS Santa Lucia Foundation, Rome 00179, Italy
  • 4Department of Neurosciences, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti 66100, Italy
  • 5Molecular Neurology Unit, Center of Excellence on Aging and Translational Medicine (Ce.S.I.-Me.T.), "G. d'Annunzio" University of Chieti-Pescara, Chieti 66100, Italy
  • 6Departments of Neurology and Pharmacology, Institute for Mind Impairments and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA
  • 7Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA
  • 8Departments of Anatomy and Neurobiology, Biochemistry and Pharmacology, University of California Irvine, Irvine, CA 92697, USA

* * Equal contribution

Received: November 21, 2018Accepted: December 6, 2018Published: January 8, 2019
https://doi.org/10.18632/aging.101719

Copyright: © 2019 Vozella 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

Circulating ceramide levels are abnormally elevated in age-dependent pathologies such as cardiovascular diseases, obesity and Alzheimer’s disease. Nevertheless, the potential impact of age on plasma ceramide levels has not yet been systematically examined. In the present study, we quantified a focused panel of plasma ceramides and dihydroceramides in a cohort of 164 subjects (84 women) 19 to 80 years of age. After adjusting for potential confounders, multivariable linear regression analysis revealed a positive association between age and ceramide (d18:1/24:0) (β (SE) = 5.67 (2.38); p = .0198) and ceramide (d18:1/24:1) (β (SE) = 2.88 (.61); p < .0001) in women, and between age and ceramide (d18:1/24:1) in men (β (SE) = 1.86 (.77); p = .0179). In women of all ages, but not men, plasma ceramide (d18:1/24:1) was negatively correlated with plasma estradiol (r = -0.294; p = .007). Finally, in vitro experiments in human cancer cells expressing estrogen receptors showed that incubation with estradiol (10 nM, 24 h) significantly decreased ceramide accumulation. Together, the results suggest that aging is associated with an increase in circulating ceramide levels, which in post-menopausal women is at least partially associated with lower estradiol levels.