Age-associated alterations in the levels of cytotoxic lipid molecular species and oxidative stress in the murine thymus are reduced by growth hormone treatment.

Autor: de Mello-Coelho V; Laboratory of Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224-6825, USA; Laboratory of Immunophysiology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil. Electronic address: coelhova@histo.ufrj.br., Cutler RG; Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224-6825, USA. Electronic address: cutlero@grc.nia.nih.gov., Bunbury A; Laboratory of Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224-6825, USA. Electronic address: calse@yahoo.com., Tammara A; Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224-6825, USA. Electronic address: Atammara0381@gmail.com., Mattson MP; Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224-6825, USA. Electronic address: mattsonm@grc.nia.nih.gov., Taub DD; Laboratory of Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224-6825, USA; Center for Translational Studies, Medical Service, VA Medical Center-DC, Washington DC, 20422, USA. Electronic address: Daniel.Taub@va.gov.
Jazyk: angličtina
Zdroj: Mechanisms of ageing and development [Mech Ageing Dev] 2017 Oct; Vol. 167, pp. 46-55. Date of Electronic Publication: 2017 Sep 01.
DOI: 10.1016/j.mad.2017.08.015
Abstrakt: During age-associated thymic involution, thymocytes decrease and lipid-laden cells accumulate. However, if and how aging affects the thymic lipid profile is not well understood, nor is it known if the hormonal milieu modifies this process. Here we demonstrate a correlation between reduced thymocyte numbers and markers of inflammation and oxidative stress with age. Evaluating the lipidomics profile of the whole thymus, between the ages of 4 (young) and 18 months (old), we found increased amounts of triacylglycerides, free cholesterol, cholesterol ester and 4-hydroxynonenal (4-HNE) with age. Moreover, levels of C24:0 and C24:1 sphingomyelins and ceramide C16:0 were elevated in 12-14 month-old (middle-aged) mice while the levels of sulfatide ceramide and ganglioside GD1a increased in the old thymus. Evaluating isolated thymocytes, we found increased levels of cholesterol ester and 4-HNE adducts, as compared to young mice. Next, we treated middle-aged mice with growth hormone (GH), which has been considered a potent immunomodulator. GH reduced thymic levels of TNF-α and 4-HNE and increased the number of thymocytes as well as the thymic levels of dihydroceramide, a ceramide precursor and autophagic stimuli for cell survival. In conclusion, GH treatment attenuated inflammation and age-related increases in oxidative stress and lipotoxicity in the thymus.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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