Scientists from Geron Corporation (Menlo Park, California) and the University Medical Center at Dallas recently reported their successful extension of the life-span of normal human cells using the enzyme telomerase. In a paper published in the January 16, 1998, issue of Science, the researchers explained that introduction of an active telomerase gene into normal mortal cells resulted in the lengthening of telomeres and a marked increase in the life-span of the cells, making the cells potentially immortal.
“This paper is a monumental advance in the understanding of the molecular genetics of aging,” remarked Leonard Hayflick, phd, professor of anatomy at the University of California, San Francisco, School of Medicine, and the discoverer of human cellular aging. “The telomerase gene will likely have many important applications in the future of medicine and cell engineering.”
Telomerase is an “immortalizing” enzyme that imparts replicative immortality when expressed in reproductive and cancer cells. Conversely, cells that do not express the enzyme are mortal. The gene for the telomerase protein was recently isolated by Geron and collaborators at the University of Colorado at Boulder.
Molecular Clock
Previous research has shown that the aging of mortal cells appears to be controlled by a molecular clock consisting of telomeres. In the report published in Science, researchers collaborated to test the effects of the immortalizing gene.
“We couldn’t be more excited about the results,” stated Wooding E. Wright, md, phd, professor in the Department of Cell Biology and Neuroscience at the University of Texas Southwestern Medical Center at Dallas and one of the authors of the paper. “I think this finally nails down the fundamental cause of cell aging, and provides a direct means of altering the clock of cell aging for therapeutic effect.”
Telomerase-Cancer Connection
In addition to its role in aging, telomerase has previously been shown to be abnormally active in all types of cancer examined and not expressed in most normal tissues. Telomerase is therefore thought to be unique among anticancer targets because it is universal across cancers and highly specific to cancer cells.
Because telomerase is required for cancer cells to proliferate indefinitely, researcher are seeking to discover new compounds that inhibit the enzyme. Such drugs are expected to lead to the death of the cancer cells through resumed telomere shortening, with little to no effect expected on normal body cells and tissues.
Significantly, the expression of telomerase in normal mortal cells extends their life-span without transforming them into malignant cancer cells, demonstrating that telomerase makes tumor cells immortal, but that other genetic alterations are responsible for the malignant characteristics of cancer cells.
“This is the best of all outcomes from our perspective” said Ronald Eastman, Geron Corporation’s chief executive officer. “These results suggest that we have a gene that is both an important target for cancer and for the treatment of age-related disease.”
Senior authors of the Science article are Dr. Wright and Dr. Serge Lichtsteiner of Geron Corporation. Coauthors from Dr. Wright’s group at the University of Texas include Drs. Shawn E. Holt, Michel Guellette, and Jerry W. Shay. Coauthors from Geron are Drs. Andrea G. Bodnar, Choy-Pik Chiu, Maria Frolkis, Calvin B. Harley, and Gregg B. Morn.
A 70-year-old man with a history of localized prostate cancer treated with whole-pelvis radiation therapy with a boost to the prostate, in conjunction with androgen deprivation therapy 7 years prior, presented with lower back pain. A bone scan revealed an area of activity in the sacrum. What is the most likely diagnosis?
