It's Not Just Lipoprotein Density - Particle Size is Important (1)

Summarized by Robert W. Griffith, MD
December 4, 2003

Introduction

Longevity is largely inherited, although a healthy lifestyle (diet, exercise, no smoking, etc) can add extra years to an individual's lifespan.

One of the lifestyle factors that's relevant is the blood lipid profile. Is it possible that there's a link between heredity factors and lipid factors? A study recently reported in JAMA has explored this, employing data from an ethnic group that's particularly long-lived.

Method

The investigators studied a group Ashkenazi Jews, whose ancestry is traced to Germany, northern France and eastern Europe. They found 213 Ashkenazi Jews who had a mean age of 98.2, and had 216 children with a mean age of 68.3 years. Physical examinations, questionnaires, and blood lipid levels from these individuals were compared with those from two carefully-selected control groups: the spouses of the offspring and other age-matched Ashkenazi Jews to reach a total of 258 subjects (mean age 70.8), and 589 subjects from the Framingham Offspring Study (mean age 67.8 years).

The blood samples were analyzed for different lipoprotein subclasses and particle sizes were measured by proton nuclear magnetic resonance. They were also examined for the presence of a variation in the CETP (cholesteryl ester transfer protein) gene that's known to be involved in the regulation of lipoprotein particle size.

Results

Both HDL and LDL particles were significantly larger in the exceptionally long-lived group and their children than in the two control groups (p=0.001 for both). The differences were independent of the actual blood levels of HDL and LDL cholesterol.

In both the offspring and the two control groups, the HDL and LDL particle sizes were significantly greater in subjects without hypertension, cardiovascular disease, or the metabolic syndrome.

Finally, the 213 subjects with exceptional longevity were found to be about 3-4 times more likely to have homozygosity for the abnormal variant of the CETP gene.

Comment

This study shows that people with exceptional longevity, and their children, have significantly larger HDL and LDL particle sizes. And this phenotype is associated with a reduced risk of hypertension, cardiovascular disease, the metabolic syndrome, and increased homozygosity for the variant CETP gene.

This study advances our knowledge of the mechanism underlying the inheritance of longevity. Moreover, taken in conjunction with another recent finding - see the companion article to this one, "It's Not Just Lipoprotein Density - Particle Size is Important (2)" - it supports the concept that, if artificial lipoprotein particles are one day used therapeutically, appropriate sizing of such particles will help prolong lifespan.

Source

• Unique lipoprotein phenotype and genotype associated with exceptional longevity. N. Barzilai, G. Atzmon, C. Schechter,  et al., JAMA, 2003, vol. 290, pp. 2030--2040

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