Abstract
BackgroundGenetic and biochemical studies have indicated an important role for lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals. This profile also coincided with a lower prevalence of disease. Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population.Methods and FindingsNMR-measured lipoprotein profiles were analyzed in 165 families from the Leiden Longevity Study, consisting of 340 long-lived siblings (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470 versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This effect was even more prominent in the long-lived siblings (p < 10−3) and could be pinpointed to a reduction specifically in the concentration of small LDL particles. No differences were observed for HDL particle phenotypes. The mean LDL particle sizes in 259 90-y-old singletons from a population-based study were similar to those in the long-lived siblings and thus significantly larger than in partners of the offspring, suggesting that the relevance of this phenotype extends beyond familial longevity. A low concentration of small LDL particles was associated with better overall health among both long-lived siblings (p = 0.003) and 90-y-old singletons (p = 0.007).ConclusionsOur study indicates that LDL particle profiles mark both familial and sporadic human longevity already in middle age.
Highlights
The study of families displaying exceptional longevity may reveal the biological basis for a healthy ageing process [1,2]
Our study indicates that low-density lipoprotein (LDL) particle profiles mark both familial and sporadic human longevity already in middle age
To assess the relevance of our findings for sporadic longevity, we studied the lipoprotein profiles in 90-y-old singletons from the general population (n 1⁄4 259; Figure 1)
Summary
The study of families displaying exceptional longevity may reveal the biological basis for a healthy ageing process [1,2]. First-degree relatives of centenarians [3] and nonagenarian siblings [4] have a lifelong mortality advantage as compared with their birth cohort These findings imply that there is a substantial familial, possibly genetic, component to exceptional longevity. Ashkenazi Jewish centenarians and their offspring have large low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles as compared with control individuals This profile coincided with a lower prevalence of disease. One study that supports this idea found that the children of 100-year-old people had larger lipoprotein particles (assemblies of proteins and fats that carry cholesterol and triglycerides in the blood) than aged control individuals. The previous study was performed in a very specific population (Ashkenazi Jewish people), and it is important to find out whether the findings are true in other populations
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