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

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.

Association between ceramides and coronary artery stenosis in patients with coronary artery disease

“…The observed association between female gender and severe coronary artery stenosis was possibly resulted from estradiol-induced unbalance of ceramides. A recent study [31] using multivariable linear regression analysis revealed that Cer (d18:1/24:0) and Cer (d18:1/24:1) were increased over age in women. In women of all ages, but not in men, plasma Cer (d18:1/24:1) was negatively correlated with plasma estradiol.…”

The imbalance in the aortic ceramide/sphingosine-1-phosphate rheostat in ovariectomized rats and the preventive effect of estrogen

“…In vitro experiments further suggested that ceramide induced vasoconstriction by iPLA2, cyclooxygenase-1 and thromboxane synthase [50]. In addition, one clinical study found a significant correlation between plasma ceramide (Cer d18:1/16:0) and hypertension in postmenopausal women [48].…”

“…The correlation between estrogen and ceramide has mainly been reported in breast cancer, serum, plasma and other tissues [46][47][48][49]. However, the effect of estrogen or ovariectomy on ceramide metabolism in vessels has never been reported.…”

Skin Aging & Modern Age Anti-aging Strategies

“…Ceramides constitute (on a weight basis) approximately 47% of the SC lipids [186]. Moisturizing treatment involves a four-step process: a) repairing the skin barrier, b) increasing water content, c) reducing TEWL and d) restoring the lipid barriers' ability to attract, hold and redistribute water.Interestingly, a statistically significant higher ceramide/cholesterol ratio was found for men than for women, as reported by Vozella et.al, 2019 [183]. Jensen et.al, 2005 reported reduced activities of ceramidegenerating epidermal acid sphingomyelinase (SMase) and ceramide synthase in the inner epidermis of aged skin, explaining its reduced capacity in barrier repair [182].…”