Lipid metabolism in long-lived families: the Leiden Longevity Study

Mechanisms underlying the variation in human life expectancy are largely unknown, but lipid metabolism and especially lipoprotein size was suggested to play an important role in longevity. We have performed comprehensive lipid phenotyping in the Leiden Longevity Study (LLS). By applying multiple logistic regression analysis we tested for the first time the effects of parameters in lipid metabolism (i.e., classical serum lipids, lipoprotein particle sizes, and apolipoprotein E levels) on longevity independent of each other. Parameters in lipid metabolism were measured in offspring of nonagenarian siblings from 421 families of the LLS (n = 1,664; mean age, 59 years) and in the partners of the offspring as population controls (n = 711; mean age, 60 years). In the initial model, where lipoprotein particles sizes, classical serum lipids and apolipoprotein E were included, offspring had larger low-density lipoprotein (LDL) particle sizes (p = 0.017), and lower triglyceride levels (p = 0.026), indicating that they displayed a more beneficial lipid profile. After backwards regression only LDL size (p = 0.014) and triglyceride levels (p = 0.05) were associated with offspring from long-lived families. Sex-specific backwards regression analysis revealed that LDL particle sizes were associated with male longevity (increase in log odds ratio (OR) per unit = 0.21; p = 0.023). Triglyceride levels (decrease OR per unit = 0.22; p = 0.01), but not LDL particle size, were associated with female longevity. Due to the analysis of a comprehensive lipid profile, we confirmed an important role of lipid metabolism in human longevity, with LDL size and triglyceride levels as major predicting factors.