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The 'Immortalizing' Enzyme:

Update on Geron Corporation

Telomerase: The 'Immortalizing' Enzyme: Update on Geron Corporation
By Saul Kent -

Life Extension Report
Vol. 15, No. 1, Janurary 1, 1995 (in Life Extension Magazine,
No. 6, April 15, 1995)

Last year, we carried an exciting report on antiaging breakthroughs at Geron Corporation in Menlo Park, California (Life Extension Report, December 1994), which is developing new therapies to treat the diseases of aging as well as aging itself. We now focus on recent advances at Geron indicating that the company is moving forward rapidly in its quest to bring laboratory breakthroughs to the marketplace.

The Function Of Telomeres

One of the major breakthroughs made by Geron scientists is the discovery of the function of telomeres, (structures at the ends of chromosomes comprised of hundreds to thousands of tandem repeats of the nucelotide sequence TTAGGG) and the role of the enzyme telomerase in maintaining the integrity of these telomeres. The reason telomeres are so important is that they are apparently critical in maintaining the structural integrity, positioning, and accuracy of replication of the chromosomes that carry the genes which serve as the blueprint for all our life functions.

Analysis has shown that in the absence of telomerase we lose 50-200 nucleotides from the telomeres at the ends our chromosomes every time one of our cells divide. This shortening of our telomeres appears to be the cellular clock that determines the number of times our cells divide which, in turn, appears to control the aging of our cells. For it is the progressive shortening of our telomeres that may be a cause (or the cause) of cellular aging, and which weakens our chromosomes to the point where cell division is no longer possible!

The Secret Of Cellular Immortality

Telomerase is a ribonucleoprotein enzyme that synthesizes telomere sequences onto the ends of our chromosomes, using a segment of its RNA component as a template. A key finding by Geron scientists is that telomerase appears to be the mechanism that stops the cellular clock of aging by maintaining telomere length and enabling cell division to continue indefinitely in cancer cells.

The ability of telomerase to maintain telomere length in cancer cells was identified by Geron scientists in lung, kidney, ovarian and other cancer cell lines, which proliferate indefinitely (see Life Extension Absracts). They also found that telomerase was not found in four normal somatic cell cultures, or in the cells of normal tissues found adjacent to the cancerous tissue from which the cells with telomerase were tested.

It has been observed for many years that cancer cells continue to divide indefinitely. As a result, they have commonly been called "immortal cells" and many scientists have speculated about why these cells are immortal. It appears as if Geron has discovered the secret of cellular immortality and is striving to exploit that secret for the benefit of all!

Geron's Unique, New Assay

Recently, Geron scientists collaborated with University of Texas researchers to develop a unique, new, highly sensitve polymerase chain reaction (PCR) assay to detect telomerase (the type of test being discussed in the O. J. Simpson case) called TRAP (Telomeric Repeat Amplication Protocol).

When combined with improvements in extraction efficacy, the TRAP assay has provided Geron with a 10,000-fold increase in the detectability of telomerase activity. The new assay has greatly reduced the number of cells required for the accurate measurement of telomerase activity. Geron used this new assay to survey a broad range of human cells and tissues for the presence of telomerase.

New Telomerase Evidence

The results of this survey were recently published in Science (Vol. 266, P. 2011-2014, Dec. 23, 1994), (see Life Extension Abstracts). The scientists found that telomerase was active in 98 of 100 immortal tumor cell lines and in 90 of 101 malignant tumor specimens, representing 12 human tumor types. As predicted, the enzyme was also shown to be present in tissue from normal ovaries and testes.

Conversely, telomerase was not found in 22 of 22 normal somatic (nonreproductive cell cultures and 50 of 50 normal or benign biopsies, representing 18 different human tissues. According to Dr. Harley, who is vice-president at Geron, "These findings provide the strongest evidence to date that telomerase is linked to cell immortality and cancer. Telomerase appears to be stringently repressed in normal human somatic tissues, but is reactivated in cancer, giving malignant cancer cells an infinite replicative capacity."

A Novel Anticancer Therapy

One of Geron's prime research goals is to develop therapies to inhibit telomerase activity in the cells of cancer patients without causing serious harm to the patient. Since telomerase appears to play no role in growth or differentiation in normal cells, a telomerase inhibitor is unlikely to interfere with these functions.

While it's true that telomerase is present in the male germ cell line it is not known whether telomerase is present in the female germ cell line (women have all their egg cells at birth). The ability to reproduce is usually not a major concern in men with cancer, who often already have children. An option in younger men that could preserve reproductive capacity would be to cryopreserve a substantial number of their sperm cells prior to treatment with a telomerase inhibitor.

Geron has developed several telomerase inhibitors, which have great promise as potential anticancer therapies and is taking steps to test these inhibitors in both animals and humans. (NOTE: Geron has INFOrmed us that they are not yet engaged in clinical testing of their telomerase inhibitors.) Geron's telomerase research could lead to the development of a universal anticancer therapy based upon basic molecular engineering, which could be useful in treating all forms of cancer!

Geron's Search For Antiaging Therapies

Geron is also conducting a search for therapies capable of stimulating telomerase activity in normal cells without triggering the uncontrolled proliferation characteristic of cancer cells. Such a therapy might prevent much of the deterioration of aging by maintaining the length of our telomeres, which would strengthen and stabilize our chromosomes. The company is also conducting research to identify all the genes involved in aging, with the aim of eventually altering their function in the quest for optimal health and longevity. We'll be reporting the results of Geron's progress in future issues of LIFE EXTENSION MAGAZINE.