~ Large Lipoprotein Particles Linked with Exceptional Longevity

The October 15 2003 issue of The Journal of the American Medical Association (http://jama.ama-assn.org/) published the results of a study of long-lived Ashkenazi Jews which found an increase in high and low density lipoprotein size in long lived members of this population as well as their offspring. Lipoproteins, composed of protein and cholesterol, are responsible for carrying fats (including cholesterol) in the blood. Small low density lipoprotein (LDL) particles more readily penetrate arterial tissue, bind more tightly and are more rapidly oxidized than large LDL lipoproteins as well as being associated with endothelial dysfunction. Small high density lipoprotein (HDL) particle size has been observed in cardiovascular disease patients, and an increased in HDL particle size as well as HDL concentration may be responsible for the benefits of exercise on cardiovascular health.

High density lipoprotein helps clear cholesterol for the vascular endothelium and peripheral tissues, and according to the authors of the article "may have systemic protective effects from lipotoxicity similar to that obtained in calorie-restricted rodents, whose life span is dramatically prolonged." HDL also has an anti-inflammatory and antioxidant effect, therefore improvements in the functionality of HDL may have a preventive effect on some of the conditions associated with aging.

Nir Barzilai, MD, of Albert Einstein College of Medicine, New York, and colleagues, studied 213 Ashkenazi Jews with an average age of 98, as well as 216 of their children whose ages averaged 68 years. Blood samples taken from the study participants, including two control groups, were analyzed for lipids, lipoprotein subclass levels and lipoprotein particle size as well as for variations in the cholesteryl ester transfer protein (CETP) gene, involved in lipoprotein particle size regulation. They found significantly increased HDL and LDL particle size among the long-lived group compared to controls as well as an increase in a specific variation in the CETP gene. In the children of the long-lived group as well as in the control populations, large HDL and LDL particle sizes were associated with a lack of hypertension, cardiovascular disease and the metabolic syndrome (syndrome X), supporting a causative relationship between particle size and longevity.

The authors write, "Individuals with exceptional longevity have been generally spared from major age-related diseases that are responsible for most deaths in elderly persons, such as cardiovascular disease, diabetes mellitus, Alzheimer disease, and cancer. Various studies suggest that genetic determinants of exceptional longevity are highly heritable. ... Identification of biological markers and genes that are conducive to exceptional longevity may provide insights into mechanisms that protect from a host of common diseases and/or slow the biological processes of aging." (JAMA. 2003; 290:2030-2040.)

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