|LEF Magazine April 1998 |
Has The Cause Of Aging
"The news is now out and it is astonishing," said Hugh Downs, co-host of ABC-TV's 20/20 program on January 16. "Researchers have discovered the mechanism that makes us age, and they claim they can slow it down."
The 20/20 show went on to tell the story of an eye-opening breakthrough by a California-based company, Geron Corporation, which was trumpeted around the world. The breakthrough involves the extension of the life span of normal human dividing cells in vitro by the introduction of the enzyme telomerase. Telomerase prevents telomere shortening, a process that has been described as the molecular clock that triggers senescence.
Telomeres are segments at both ends of gene-carrying chromosomes in the cell nucleus that maintain the integrity of the chromosomes. Normal dividing cells grow old and sluggish. Eventually they stop dividing because they lack telomerase to keep their telomeres from shortening, which weakens their chromosomes. Cancer cells, on the other hand, which have a plentiful supply of telomerase, continue dividing indefinitely, but are abnormal. The continuous, rapid division of abnormal cancer cells is a lethal process that leads, if unchecked, to the death of the organism.
"We believe that telomerase therapy will provide ground-breaking advances within the next 5 to 10 years for the treatment of the diseases of aging."
The great achievement of the Geron scientists was their ability to use telomerase to induce normal cells to continue dividing long after normal cells without telomerase had stopped dividing, but without transforming them into abnormal cancer cells. The telomerase-laden cells exceeded their normal replicative life span by at least 20 doublings.
The research team, which included scientists at Southwestern Medical Center in Dallas, concluded that "the ability to maintain normal human cells in a . . . youthful state may have important applications in research and medicine." Among the medical applications mentioned in their paper in Science magazine (www.sciencemag.org) are rejuvenation of atrophying skin, reversal of age-related macular degeneration of the eye, and halting atherosclerosis caused by loss of endothelial cell proliferation.
In order for Geron's method of keeping cells youthful to be clinically applicable for the treatment of age-related diseases in humans, it will be necessary to show that it can be used therapeutically in humans. It may be that perhaps aging human cells can be induced by introduction of the gene for telomerase to remain youthful in living human beings, not just in artificially maintained cell cultures in the laboratory.
At the Life Extension Foundation, we believe that this will be achieved, and that telomerase therapy will provide ground-breaking advances within the next five to 10 years for the treatment of the diseases of aging. If this occurs, it may be the impetus for spectacular advances in combating lethal killers such as atherosclerosis, diabetes, arthritis, Alzheimer's disease and Parkinson's disease. We also believe that Geron will develop a method of inhibiting telomerase expression in cancer cells, which will prove extremely valuable in treating cancer.
However, we are more skeptical about the view presented in the 20/20 story and elsewhere that Geron has made the first step in developing a "fountain of youth," which will enable us to live for centuries. On 20/20, Dr. Michael West, Geron's founder (who is currently the company's Vice President for New Technologies), says, "If ever there was a technology that could extend life span, I think this would be it." And Dr. Michael Fossel (the editor of Mary Ann Liebert Inc.'s new Journal Of Anti-Aging Medicine) predicts that telomerase therapy will lead to "life spans of several hundred years . . . healthy life spans."
This is highly uncertain because of the fact that preventing dividing cells from growing old is just part of the story. For the fact of the matter is, there are critically important cells within the body that do not divide, such as neurons and muscle cells. These also include cells in the brain that are involved in the regulatory mechanisms that control such essential life functions as information processing, learning and memory, reproduction, sleep, temperature, appetite, sex drive, mood and more.
These life processes all are affected by caloric restriction, which is the only proven method of extending maximum life span. It remains to be seen whether maintaining youthful dividing cells will, in itself, be sufficient to slow aging and extend life span in the entire organism.
On the other hand, it may be that if we ultimately are able to maintain youthful dividing cells in the brain (the glial cells)-cells which greatly outnumber neurons-will be able to keep brain neurons in a youthful state by providing a better support system for them. After all, glial cells provide neurons with nutritional and other types of support required for optimal function. Moreover, while neurons don't divide, the intracellular components within them are replenished on a regular basis with the help of glial cells.
These questions and many more will require extensive future research, which Geron scientists (and others) will likely be conducting. In any case, the Geron breakthrough is likely to lead to many important therapeutic advances in the relatively near future, and is an important milestone in our quest to control aging and live longer, healthier lives.
Saul Kent, President
Life Extension Foundation