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To compare the change in lipoprotein metabolism with aging, we analyzed the lipid and protein compositions of individual lipoprotein fractions. Healthy and nonobese elderly participants (elderly group, n = 26) had a serum lipid profile within the normal range, although slightly higher than in young participants (control group, n = 18). However, the elderly group had a twofold higher serum uric acid level and triglyceride (TG):high-density lipoprotein cholesterol ratio. The elderly group had less antioxidant ability and elevated TG content in high-density lipoprotein (HDL) with enhanced cholesteryl ester transfer activity. An elevated level of advanced glycated end products in lipoproteins and fragmentation of apoA-I were present in the elderly group, with detected lower apoA-I level and more multimerized apoA-I in HDL. The protein levels of apoA-I, apoC-III, and serum amyloid A in lipoprotein-deficient serum were increased in the elderly group.

High-density lipoprotein (HDL) is a strong antioxidant, anti-inflammatory, and antisenescence molecule. However, in the current study, HDL from the elderly group (E-HDL) exhibited increased glycation with apolipoprotein (apo) A-I multimerization and decreased phospholipid content. Similarly, glycated apoA-I (gA-I) by fructosylation has a covalently multimerized band without a crosslinker and impaired phospholipid-binding ability. Treatment of human dermal fibroblasts and macrophages with E-HDL and gA-I caused more severe cellular senescence and foam cell formation, respectively; however, treatment with HDL from a young group (Y-HDL) and native apoA-I (nA-I) suppressed senescence and atherosclerosis. E-HDL(3) and reconstituted HDL (rHDL) containing gA-I showed enhanced cholesterol influx into macrophages compared with Y-HDL(3) and nA-I-rHDL. In conclusion, E-HDL and gA-I-rHDL share similar physiologic properties in macrophages and human dermal fibroblasts. E-HDL and gA-I-rHDL exacerbated cellular senescence and atherosclerosis with increased cellular cholesterol influx.

Until now, there has been limited information on the effects of smoking on atherogenesis and senescence in the context of lipoprotein parameters, particularly in young smokers who have smoked fewer than 10 cigarettes per day for 3 years. In this study, lipoprotein profiles and functions were compared between smoker (n = 21) and control groups (n = 20). In the smoking group, ferric ion reduction abilities of serum and high-density lipoprotein (HDL) fractions were significantly reduced, and low-density lipoprotein (LDL) was severely oxidized. All lipoprotein particles from the smoker group showed higher advanced glycated end products with more triglyceride (TG) content compared with the control group. Lipoproteins from smokers showed faster agarose gel electromobility as well as greater smear band intensity in SDS-PAGE due to oxidation and glycation. LDL from smokers was more sensitive to oxidation and promoted foam cell forma-tion in macrophages. Gel filtration column chromatography revealed that the protein and cholesterol peaks of VLDL and LDL were elevated in the smoker group, whereas those of HDL were reduced. Human dermal fibroblast cells from the smoker group showed severe senescence following treatment with HDL2 and HDL3. Although HDL from young smokers showed impaired antioxidant ability, smaller particle size, and increased TG content, cholesteryl ester transfer protein activities were greatly enhanced in the serum and HDL fractions of the smoker group. In conclusion, smoking can cause production of dysfunctional lipoproteins having a smaller particle size that exacerbate senescence and atherogenic progress due to oxidation and glycation.