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.

中文翻译：

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通过生长激素治疗，可以减少小鼠胸腺中细胞毒性脂质分子种类和氧化应激的年龄相关变化。

在与年龄相关的胸腺复性过程中，胸腺细胞减少并且脂质负载的细胞积累。然而，关于衰老是否影响胸腺脂质分布以及如何影响胸腺脂质分布的了解尚不清楚，也不知道激素环境是否会改变这一过程。在这里，我们证明了胸腺细胞数量减少与炎症和氧化应激标志物之间的相关性。在评估4岁（年轻）至18个月（大）之间的整个胸腺的脂质组学概况时，我们发现随着年龄的增长，三酰甘油酯，游离胆固醇，胆固醇酯和4-羟基壬烯醛（4-HNE）的含量增加。此外，在12-14月龄（中年）小鼠中，鞘磷脂和C24：0和神经鞘氨醇C16：0的水平升高，而在老胸腺中，硫化物神经酰胺和神经节苷脂GD1a的水平升高。评估分离的胸腺细胞，我们发现与年轻小鼠相比，胆固醇酯和4-HNE加合物的含量增加了。接下来，我们用生长激素（GH）治疗中年小鼠，该激素被认为是有效的免疫调节剂。GH降低了TNF-α和4-HNE的胸腺水平，并增加了胸腺细胞的数量以及二氢神经酰胺，神经酰胺前体和自噬刺激物的胸腺水平，以维持细胞存活。总之，GH治疗减轻了炎症，并引起了与年龄相关的胸腺氧化应激和脂毒性增加。神经酰胺前体和细胞自噬刺激。总之，GH治疗减轻了炎症，并引起了与年龄相关的胸腺氧化应激和脂毒性增加。神经酰胺前体和细胞自噬刺激。总之，GH治疗减轻了炎症，并引起了与年龄相关的胸腺氧化应激和脂毒性增加。