Studies Lift Hopes for Anti-Aging Technology / `Immortality' enzyme doesn't cause cancer
New studies of a so-called immortality enzyme suggest that it can be safely used to extend the life span of human cells without making them cancerous.
The findings, published in the latest issue of the journal Nature Genetics, are based on a yearlong study of the enzyme telomerase in human skin and retina cells that were transplanted into laboratory mice.
Results appear to resolve one of the key safety issues that had kept researchers from testing the anti-aging technology in people. If further tests succeed, telomerase genes might be used to counteract the normal aging process, allowing possible treatments for common aging-related conditions, such as failing eyesight and wrinkled skin.
A year ago, telomerase was shown in test-tube studies to give cells that normally wear out and die after a few reproductive cycles a virtually limitless capacity to divide and multiply.
The early findings generated considerable fanfare but also raised concerns that the same enzyme, which is linked to many forms of cancer, might trigger runaway growth in otherwise benign, albeit tired, cells.
The latest mouse experiments were designed to address these concerns. The studies of human cells were done in mice with bioengineered humanlike properties -- the closest thing to a human trial as could be safely devised at this stage.
The work was sponsored by Geron Corp., a Menlo Park-based biotech company seeking to commercialize the telomerase technology. Along with Geron researchers led by Choy-Pik Chiu, scientists involved in the work included Geoffrey Wahl at the Salk Institute in La Jolla and Thea Tisty at the University of California at San Francisco.
Similar results, reported separately in the same science journal, were obtained by a team of Geron collaborators at the University of Texas Southwestern Medical Center in Dallas.
Calvin Harley, chief scientific officer at Geron, said the bioengineered "immortal" cells are still growing in the lab mice and, by all indications, "these cells are behaving like normal cells."
All the usual mechanisms for arresting cancerous growth appear to be working, he added, suggesting that the presence of the telomerase, by itself, is not enough for tumors to form.
The aging process occurs when cells exhaust their supply of "telomeres" -- bits of genetic material that give cells the instructions needed to keep dividing into new copies.
SHOELACES AND DNA
Like plastic tips on shoelaces, the telomeres are found at the ends of the long stretches of DNA packed into each cell's nucleus. In essence, the tips of telomeric DNA wear away each time the cell reproduces, until none is left.
Except during the fetal stage of development, most cells typically lack the active gene needed to make new DNA tips. The telomerase enzyme, a protein expressed by this gene, is what gives cells that ability. It is also one of the factors in malignancies, where cell growth runs amok.
Evidence that the enzyme can be used as a potential therapy without triggering unregulated growth still leaves some safety questions unanswered. Chief among them is whether cancerous properties might emerge after a longer period of time.
Nevertheless, the latest studies pave the way for rigorous preclinical experiments -- the final stage before the technology might be tried in a few test subjects.
Geron hopes the telomerase technology can play a role in a host of drug development and gene therapy efforts, where it's often useful to keep cells alive for extended periods of time. Two of the most promising applications include telomerase in bioengineered cells from bone marrow and blood.
Ultimately, the gene that encodes telomerase might be inserted into certain cells in humans to reverse the aging process. But the first stage of human testing is two to three years away, if all goes well.