Cholesterol: Size Does Matter (1)

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

Introduction

It's undeniable that longevity runs in families, so it may seem that there's nothing much that you can do about living longer. However, if you read these pages often, you'll know that a healthy lifestyle (eating right, exercising regularly, not smoking, etc) can add extra years to your lifespan.

One of the factors worth watching in your lifestyle measures is your lipid profile - especially your low-density lipoprotein (LDL) cholesterol, and your high-density lipoprotein (HDL) cholesterol levels. We all know now that a high LDL level is bad, and a high HDL level is good, when it comes to the risk of heart attacks and so on.

LDL particles have more fat and less protein than HDL, and they tend to stick to the cells lining the blood vessels. HDL particles, on the other hand, move more freely through the blood vessels, and carry cholesterol away from the arteries and back to the liver. Being denser, HDL particles are, in fact, smaller than LDL particles.

Now a study published in the Journal of the American Medical Association has tried to show if genetic factors for long life are linked in any way to the proportion of different density cholesterols in the body. And one of the things they measured was particle size.

What was done

To study this problem, the investigators selected a group of people some of whom have exceptional longevity - Ashkenazi Jews, whose ancestry is traced to Germany, northern France and eastern Europe. They found 213 Ashkenazi Jews who had an average age of 98, and had 216 children with an average age of 68. Physical examinations, questionnaires, and blood lipid levels from these individuals were compared with those from two carefully-selected control groups: 258 Ashkenazi Jews of a similar age and gender as the children in the first group, and 589 same-aged subjects from the Framingham Offspring Study.

The blood samples were analyzed for the different lipoprotein subclasses (there are more than just HDL and LDL) and particle sizes were measured by a technique known as proton nuclear magnetic resonance. They were also examined for the presence of a variation in one precise gene (CETP or cholesteryl ester transfer protein) that's involved in the regulation of lipoprotein particle size.

What was found

Both HDL and LDL particles were significantly larger in the exceptionally long-lived group and their children than in the two control groups. 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 particles were significantly larger in people who didn't have high blood pressure, cardiovascular disease, or the metabolic syndrome (syndrome-X or the insulin-resistance syndrome).

Finally, the 213 subjects with exceptional longevity (the 98-year-old parents) were found to be about 3-4 times more likely to have 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 means a lesser risk of high blood pressure, heart disease, and the metabolic syndrome.

Does this finding have practical implications? Not immediately; it merely advances our knowledge of the mechanism underlying the inheritance of longevity. However, taken in conjunction with another recent finding - see the companion article to this one, "Cholesterol: Size Does Matter (2)" - it supports the idea that one day, artificial lipoprotein particles may be used therapeutically, and appropriate sizing of these particles may help prolong the natural 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

Related Links
Cholesterol: Size Does Matter (2)
Two Serious Effects of the Metabolic Syndrome
Tool: Do You Have the Metabolic Syndrome (Syndrome X)?

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