Simin Nikbin Meydani, Director of the Human Nutrition Research Center on Aging, with HNRC staff, Alberto Molano, Angelo Azzi, Dayong Wu, and Zhaofeng Huang, as well as Melissa G. Marko, PhD candidate, and Stephen C. Bunnell, associate professor of pathology, published Age-dependent changes in the sphingolipid composition of mouse CD4+ T cell membranes and immune synapses implicate glucosylceramides in age-related T cell dysfunction in PLoS One in October 2012. The article abstract is below –
To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4+ T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4+ T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4+ T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4+ T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4+ T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4+ T cell function.