More Secrets to Cellular Aging Revealed

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More Secrets to Cellular Aging Revealed

Cosmiverse.com

June 15, 2001

Scientists at the UT Southwestern Medical Center at Dallas have found that genes

located near human telomeres can be

silenced. The discovery may help explain how and why humans age. Telomeres are

repeating sequences of DNA located at the

end of each chromosome and are thought to function as a counting mechanism for

cellular aging. Dr. Jerry Shay and Dr.

Woodring , UT Southwestern professors of cell biology, report in the

current issue of Science that human cells can

exhibit telomere position effect (TPE), a mechanism by which genes near

telomeres can be turned off, and that the

strength of gene silencing is proportional to the length of nearby telomeres.

Each time a mortal cell divides, its telomeres become shorter. When they reach a

preset length, the cell ceases to

divide, ages and dies.

Shay and , along with collaborators at UT Southwestern, have already shown

that human cells age every time they

divide because their telomeres shorten. After a finite number of cell divisions

- when telomeres become short - the

cells stop dividing. Most normal cells lack the enzyme telomerase, which

maintains telomeres. Telomerase is activated in

90 percent of all cancers, in which cells continue to divide at a high rate.

Many diseases, such as Down syndrome, are

characterized by premature aging. A greater understanding of TPE could help

researchers discover how cellular aging

contributes to the overall aging process.

" This is an important step in trying to explain the connection between telomere

shortening and aging, " Shay said.

" Normal cells will only grow for a limited time. They grow for a while, and then

they go through a process called

senescence, or aging. We wanted to know about the molecular memory. Are cells

counting how many times they divide? We

believe the telomeres are the molecular memory. "

The researchers placed DNA containing a luciferase (the enzyme that allows

fireflies to emit light) gene into human

cells and showed that if it became located at the telomere, there was 10 times

less luciferase activity than if it was

located in the middle of a chromosome. They also found an even greater decrease

in luciferase activity if they used

telomerase to make the telomeres grow longer.

" We knew that when telomeres became too short, they caused cells to stop

dividing, but there wasn't a mechanism for how

a cell could sense how long its telomeres were before they became too short. TPE

can do that. It can let a cell know how

old it is so that it could change its behavior before it became senescent, " said

.

TPE could also help to explain the differences between young and old cells. For

example, " aging " genes next to telomeres

would be silent when the cells were young. As the cells aged and continued to

divide, their telomeres would shorten; the

silencing of the genes would be reversed; and the " aging " genes activated. The

researchers are now trying to find

naturally occurring human genes located near telomeres whose expression is

influenced by telomere length. ph A.

Baur, a UT Southwestern student research assistant in cell biology, and Dr. Ying

Zou, a UT Southwestern cell biology

fellow, were also part of the research.

Shay and 's earlier research has shown that telomerase causes human cells

grown in the lab to retain their " youth "

and continue to divide long past the time when they normally should stop

dividing. Figuring this out has made the use of

normal cells for tissue engineering and other therapeutic uses much easier.

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Here we see that as the telomere in our cells shortens (due to cellular

division), it makes the cell act " Older " as the

genes located near the ends of the chromosome become less and less capable of

" Normal / Youthful " operation.

Taking this to the next step might suggest that boosting cellular growth may

actually accelerate aging. Ouch.....

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Good Health & Long Life,

Greg ,

http://www.ozemail.com.au/~gowatson

gowatson@...