- DALLAS -- Researchers at UT Southwestern Medical Center at Dallas and
their colleagues at Geron Corp., Menlo Park, Calif., say they have figured
out how to overcome the mechanisms that control cellular aging and extend
the life span of human cells.
- In the Jan. 16 issue of Science, Drs.
Woodring Wright and Jerry Shay, UT Southwestern professors of cell biology
and neuroscience, and their collaborators report finding that the enzyme
telomerase -- which UT Southwestern scientists call a "cellular fountain
of youth" -- causes human cells grown in the laboratory to retain
their "youth" and continue to divide long past the time when
they normally stop dividing.
- Normal human cells have a limited capacity
to proliferate. After a certain finite number of cell divisions, time on
the biological clock runs out; the cells "age" and stop dividing.
Time remaining in a cell's life correlates with the length of the telomeres
-- repeated sequences of DNA on the ends of chromosomes that protect the
tips from degradation. In normal cells, telomeres shorten with each cell
division. Although some have thought that this telomere shortening might
be the biological clock's control mechanism, the hypothesis was controversial.
The research now proves that human cells grow older each time they divide
because their telomeres shorten.
- Specialized reproductive cells and most
cancer cells appear to divide indefinitely. They contain the enzyme telomerase,
which adds back telomeric DNA to the ends of chromosomes. Most normal cells
do not have this enzyme.
- "We have found that cellular aging
can be bypassed by the introduction of the catalytic component of the immortalizing
enzyme telomerase," Shay said. "The expression of telomerase
LIFE SPAN -- 2in normal human cells should extend their lifespan indefinitely.
From a basic research point of view, we could begin to replace the abnormal
tumor-cell lines now being used to study biochemical and physiological
aspects of growth and differentiation with normal, yet immortal cell lines."
- The scientists introduced telomerase
into normal human cells to see if the cells' life spans could be prolonged.
The cells with telomerase extended the length of their telomeres, divided
for 20 additional generations past the time they normally would stop dividing
and are continuing to divide. The cells also grew and divided in a normal
manner, giving rise to normal cells with the normal number of chromosomes.
By all accounts these cells had found their fountain of youth.
- "The extension of normal cell lifespan
in a youthful state by telomerase is a dramatic confirmation of the telomere
hypothesis and one that presents numerous opportunities for biotechnology
and medicine," said Dr. Calvin Harley, Geron vice president and chief
- One immediate use of finding that telomere
shortening controls cellular aging may be in the area of producing engineered
products in human cells. Instead of using uncharacterized primary human-cell
cultures to produce vaccines or other biological products, one should now
be able to produce products in a re-engineered normal human cell-type that
does not change, Wright said.
- "This research raises the possibility
that we could take a patient's own cells, rejuvenate them, then modify
the cells as needed and give them back to the patient to treat a variety
of genetic and other diseases," Wright said. "The potential long-term
applications are simply staggering."
- Other investigators on the project included
Drs. Andrea Bodnar, Maria Frolkis, Choy-Pik Chiu, Gregg B. Morin, Calvin
Harley and Serge Lichtsteiner of Geron Corp.; and Drs. Michel Ouellette
and Shawn Holt, research fellows in UT Southwestern's Department of Cell
Biology and Neuroscience. The research was funded in part by the National
Institutes of Health.