lipoprotein size and longevity

[Guest guest]

An interesting article in today's NY Times

http://www.nytimes.com/2003/10/15/science/15OLD.html

October 15, 2003

Living Longer and Larger: It's in the Size of Cholesterol-Carrying Molecule=

s

By MARY DUENWALD

Scientists trying to figure out why just 1 person in 10,000 lives to be 100=

have

found an important clue in the blood.

Centenarians, a new study shows, tend to have larger than average

cholesterol-carrying molecules.

The study, to be published today, in The Journal of the American Medical

Association, adds to an emerging collection of evidence that suggests that =

the

size of lipoproteins, both good and bad, may play a significant role in hea=

rt

disease, diabetes and, consequently, longevity.

" Large particle size seems to give people an extra 20 years of life, with v=

ery

little disability to go along with it, " said Dr. Nir Barzilai, who directed=

the study

at the Albert Einstein College of Medicine in the Bronx.

Dr. Barzilai also traced large lipoproteins to a specific gene that influen=

ces

lipoprotein size.

The study looked at 213 centenarians and 216 of their offspring, as well as=

a

control group of 256 people in their 60's and 70's whose parents did not li=

ve

to 100. The three groups were similar in their average total cholesterol; i=

n

their bad cholesterol, or low density lipoproteins; and in their body mass =

indexes, which are based on a ratio of height and weight and are used to

gauge whether people are overweight. The centenarians and offspring, as

would be expected, had higher levels of the good cholesterol.

But when the researchers looked at lipoprotein size, the centenarians stood=

out. Eighty percent of them were found to have an unusually high proportion=

of large particles. Nearly half of their children also had the large partic=

les,

suggesting an even chance of inheriting the quality, Dr. Barzilai said. Jus=

t 8

percent of the control group had the larger lipoproteins.

The researchers also found that subjects with cardiovascular problems were =

less likely to have large lipoproteins.

" It's no surprise that centenarians would be specially protected against

cardiovascular disease, " said Dr. T. Perls, a geriatrician at the Bo=

ston

Medical Center who directs a separate study of centenarians. " It's the No. =

1

killer among old people, and centenarians must have some protection against=

it. "

Another centenarian researcher, Dr. W. Vaupel, director of the Max

Planck Institute for Demographic Research in Rostock, Germany, cautioned

against overinterpreting the new study.

Smaller lipoprotein size " looks to be a risk factor for cardiovascular dise=

ase, "

Dr. Vaupel said. " But there are many other risk factors — high blood pressu=

re,

smoking, eating a fatty diet, not getting enough exercise. "

In the last five years, other researchers have also found a connection

between small molecules of the bad cholesterol, or L.D.L., and the perilous=

buildup of plaques in the arteries. Small L.D.L. particles are better at di=

gging

into the walls of blood vessels and creating the conditions for plaques to =

form,

said Dr. W. Garvey, chairman of nutrition sciences at the Universit=

y of

Alabama at Birmingham School of Medicine, who has conducted some of this

research.

" All L.D.L. particles are bad, " Dr. Garvey said. " But the smaller ones are =

worse

than the bigger ones. "

When people who have been sedentary start performing regular exercise,

their L.D.L. particles grow bigger, as shown by Dr. E. Kraus, a

cardiologist at the Duke University Medical Center, and his colleagues a ye=

ar

ago in a study of people 40 to 65.

" For years, " Dr. Kraus said, " scientists had known that exercise helped

prevent heart disease. But we didn't know how it could be beneficial, becau=

se

it didn't affect cholesterol levels. Now we know that exercise makes small =

dense L.D.L. particles larger and fluffier. "

How size affects the operation of the good cholesterol, or high density

lipoproteins, is not known. H.D.L. carries cholesterol out of the blood ves=

sels

and into the liver. One possibility is that the larger H.D.L. molecules sim=

ply

carry a bigger load. But, Dr. Barzilai said, " The situation may be more

complex. "

He traced the larger particles from a mutation in a gene that is responsibl=

e for

creating a protein, C.E.T.P., or cholesterol ester transfer protein, which =

helps

regulate the size of cholesterol particles. Dr. Barzilai found that nearly =

25

percent of the centenarians in his study carried two copies of a particular=

variant of the gene that suppresses C.E.T.P. activity. In the control group=

, just

8 percent had the variant.

The gene may be one reason why some centenarians in Dr. Barzilai's study

have lived to 100, even though they were overweight or ate badly.

" I hate to say it, " he said. " but I think it's true. If you have this gene,=

you can

smoke and you can be fat and you can not exercise. This sounds to me

terrible. "

Dr. Barzilai suspects that perhaps four or five other genes also have roles=

in

determining lipoprotein size. He said he had begun to zero in on a second

gene that appears to be as important as the C.E.T.P. gene.