Genes and Longevity (Published October 20, 2003)

Most people know that if you pick your parents carefully for a family history of longevity, the odds are that you, too, will live a long life. What it is exactly that can be passed down to children to increase the probability of exceptional longevity has never been quite clear.

A small, but intriguing study reported in the Journal of the American Medical Association last week may have shed some light on genetic markers of long life. This study demonstrated that certain blood fat particle characteristics seemed to be more prevalent in long-lived individuals and that these blood fat characteristics were heritable. That is, the genes for healthy aging could be passed down generations.

Terrific. But what does this really mean to you? We have to look at how the results were gathered, what was measured, and then determine if the conclusions are transferable to the general population.

The investigators looked at a relatively small group of 213 Ashkenazi Jewish individuals who lived very long lives, on average 98 years plus/minus 5 years, and also looked at their children. The researchers then age-matched them with other Ashkenazi Jews and individuals from the Framingham Offspring Study that I have discussed in prior columns. Questionnaires, physical examinations and analysis of blood fat levels and characteristics as well as DNA analysis of blood fat regulating genes were obtained.

What this research demonstrated was that individuals and their children that lived the longest had significantly larger sized blood fat particles of the HDL-cholesterol (good cholesterol) and LDL-cholesterol (bad cholesterol) types, as well as a form of the regulating blood fat gene shown to produce larger blood fat particles.

Much of this is not new information. It has been known for decades that all HDL-cholesterol and LDL-cholesterol particles are not alike. There are at least four classes of HDL and at least seven classes of LDL, plus varying subtypes. These groups vary by fat and protein content as well as particle size. Larger LDL particles, called the “fluffy, puffy”, have long been associated with less harm to the blood vessels than the “small, dense” LDL particles. The smaller size particles have been thought to be more susceptible to oxidation and thus trigger more inflammatory and immunogenic responses from the body that may damage blood vessels. Mechanically, the smaller sizes may also facilitate entry of the particles into the blood vessel walls. The HDL particle sizes are trickier to interpret since HDL size varies with maturity of the particle and what that HDL particle is doing at any specific time in the transfer of cholesterol from place to place.

So, should you go out and have your particles measured? If knowing your particle size will cause undue elation or abject depression, perhaps you should hold off. And unless you are an Ashkenazi Jew, the results may not be applicable anyway since there may be other, unmeasured interactions that produce longevity in that specific population.

Also, knowing your particle size would be useful if you could change it favorably. Do not forget that this was a genetic study, not a drug or lifestyle intervention study that showed some intervention changing the course of a disease process.

There are medications that can convert small, dense LDL-cholesterol particles toward the fluffy, puffy side of the spectrum, especially if another blood fat called triglycerides is elevated. Statins, niacin and fibrates tend to move smaller, bad LDL particles to larger, less bad particles sizes. The proper medication choice should be discussed with your doctor. And the Ventura Heart Institute may be involved with upcoming new classes of drugs that will regulate particle size directly. But you don’t always have to rely on medications to do this.

Lifestyle changes can also make smaller LDL cholesterol particles larger and raise levels and increase the size of HDL cholesterol particles. Weight loss, exercise and alcohol restriction can effect these beneficial changes. Reducing oxidative stresses on the particles is important as well, so cigarettes are definitely bad.

So this report adds interesting information on how longevity may be passed on. But you should take away from this study that those identified factors can be modified by healthy lifestyle changes. And if those changes are not adequate, judicious supplementation by properly selected medications may do the trick.



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