ABSTRACT
BACKGROUND: Aging is associated with a decline in lymphocyte function however, little is known about dendritic cell (DC) subsets and aging. Aging is also associated with increasing circulating lipid levels and intracellular lipid accumulation modulates DC function. Whether age-associated increases in lipid levels influence DC biology is unknown. Thus, the effects of aging on DC subsets were assessed in vivo using young adult and elderly C57BL/6 J mice. RESULTS: Major age-related changes included increased CD11c(+) DC numbers in lymph nodes, spleens and livers, but not lungs, and significantly increased proportions of plasmacytoid (pDC) and CD4(-)CD8α(+) DCs in lymph nodes and livers. Other changes included altered pDC activation status (decreased CD40, increased MHC class-I and MHC class-II), increased lipid content in pDCs and CD4(-)CD8α(+) DCs, and increased expression of key mediators of lipid uptake including lipoprotein lipase, scavenger receptors (CD36, CD68 and LRP-1) in most tissues. CONCLUSIONS: Aging is associated with organ-specific numerical changes in DC subsets, and DC activation status, and increased lipid content in pDCs and CD4(-)CD8α(+) DCs. Up-regulation of lipoprotein lipase and scavenger receptors by lipid-rich pDCs and CD4(-)CD8α(+) DCs suggests these molecules contribute to DC lipid accumulation in the elderly. Lipid accumulation and modulated activation in pDCs and CD4(-)CD8α(+) DCs may contribute to the declining responses to vaccination and infection with age.
ABSTRACT
BACKGROUND: Polymorphism in the gene for apolipoprotein E (apo E) influences lipid metabolism. Relative to the epsilon3 allele, the epsilon4 allele tends to increase and the epsilon2 allele tends to decrease total and serum cholesterol, but uncertainty remains concerning an influence on the risk of coronary artery disease (CAD). It is possible that the influence of apo E alleles on CAD risk is influenced by the age of subjects studied. In this study, we examine the influence of the epsilon2 and epsilon4 alleles on the risk of CAD in relatively young subjects. METHODS: We determined the apo E genotype of 564 Caucasian CAD subjects below 50 years of age presenting with symptomatic CAD, either with or without prior myocardial infarction, and documented by angiography, and 639 similarly aged Caucasian control subjects without symptomatic CAD randomly selected from the community. RESULTS: The frequency of subjects with the epsilon2/3 genotype was significantly lower in CAD subjects than controls (6 vs. 11%, P<0.01) and, relative to epsilon3/3, the epsilon2/3 genotype was associated with a significant reduction in total and LDL-cholesterol in male and female control subjects. In contrast, there was no difference in the frequency of epsilon4/4 or epsilon4/3 genotypes in CAD cases and controls (30 vs. 26%, NS), and the latter genotypes had little influence on total or LDL-cholesterol. CONCLUSION: The results indicate a beneficial effect of the epsilon2/3 genotype not only on LDL cholesterol but in decreasing the risk of CAD in Caucasians at a young age.
