Vozella Valentina, Basit Abdul, Piras Fabrizio, Realini Natalia, Armirotti Andrea, Bossù Paola, Assogna Francesca, Sensi Stefano L, Spalletta Gianfranco, Piomelli Daniele
Department of Drug Discovery and Development, Italian Institute of Technology, Genova 16163, Italy.
Department of Clinical and Behavioral Neurology, Laboratory of Neuropsychiatry, IRCCS Santa Lucia Foundation, Rome 00179, Italy.
Aging (Albany NY). 2019 Jan 8;11(1):73-88. doi: 10.18632/aging.101719.
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); = .0198) and ceramide (d18:1/24:1) (β (SE) = 2.88 (.61); < .0001) in women, and between age and ceramide (d18:1/24:1) in men (β (SE) = 1.86 (.77); = .0179). In women of all ages, but not men, plasma ceramide (d18:1/24:1) was negatively correlated with plasma estradiol (r = -0.294; = .007). Finally, 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.
在心血管疾病、肥胖症和阿尔茨海默病等与年龄相关的病症中，循环神经酰胺水平异常升高。然而，年龄对血浆神经酰胺水平的潜在影响尚未得到系统研究。在本研究中，我们对164名年龄在19至80岁之间的受试者（84名女性）组成的队列中的一组特定血浆神经酰胺和二氢神经酰胺进行了定量分析。在对潜在混杂因素进行校正后，多变量线性回归分析显示，年龄与女性体内神经酰胺（d18:1/24:0）（β（标准误）= 5.67（2.38）；P = 0.0198）和神经酰胺（d18:1/24:1）（β（标准误）= 2.88（0.61）；P < 0.0001）呈正相关，在男性中年龄与神经酰胺（d18:1/24:1）呈正相关（β（标准误）= 1.86（0.77）；P = 0.0179）。在所有年龄段的女性中，而非男性中，血浆神经酰胺（d18:1/24:1）与血浆雌二醇呈负相关（r = -0.294；P = 0.007）。最后，在表达雌激素受体的人类癌细胞中进行的实验表明，用雌二醇（10 nM，24小时）孵育可显著降低神经酰胺的积累。总之，结果表明衰老与循环神经酰胺水平升高有关，在绝经后女性中，这至少部分与较低的雌二醇水平有关。
