November 13, 2008
New HIV Treatment May Also Slow Aging Process
A drug derived from a plant used in Chinese medicine has shown promising results in fighting HIV and has possible applications in slowing the aging process.
Scientists hope the drug may work to shorten telomeres, "caps" found at the end of chromosomes that get shorter as cells age. The telomeres are believed to affect the lifespan of cells. These DNA caps can be regenerated with an enzyme known as telomerase, and although it has never been tested, some believe it might be possible to extend longevity by increasing telomerase production.Rita Effros at the University of California in Los Angeles (UCLA) has successfully used a drug that increases telomerase to improve the immune response to viruses.
In previous work, Effros and her colleagues inserted a portion of the telomerase gene into killer T-cells, immune cells that fight infections, and found that the drug had strengthened the anti-viral activity of these cells. However, such gene therapy is not a sensible method to treat the millions of people infected with HIV.
In her current study, Effros took killer T-cells from HIV-infected people and exposed them to TAT2, a drug developed by Menlo Park, Calif.-based Geron Corporation that is believed to increase telomere production. The drug is derived from the root extract of a plant called Astragalus, which is traditionally used in Chinese medicine to boost the immune system.
Effros' study found that TAT2 reduced telomere shortening, increased the ability of cells to divide, and supercharged their antiviral activity. Furthermore, this effect was blocked when a second drug was used to inhibit telomerase, suggesting that TAT2 was truly working through the enzyme. However, the underlying mechanism that makes the drug work is not yet thoroughly understood.
"It is beginning to look like telomerase is doing more than just keeping telomeres from getting too short," Effros told New Scientist magazine.
"It seems to be mediating some anti-viral mechanisms as well."
Indeed, previous studies have found that people with HIV who go years without developing AIDS have killer T-cells with high telomerase activity and longer telomeres.
Ultimately, Effros hopes that TAT2 might be used as a supplement to existing anti-retroviral drugs to boost the immune systems of those with HIV.
Aubrey de Grey of the Methuselah Foundation, which promotes research into lifespan extension, praised the study as a significant step forward.
"It is what we would have hoped," he told New Scientist.
"We've thought for some time that, by activating telomerase in these cells, we could extend their proliferative capacity. What was completely unclear was whether that would [have negative side effects]. These cells become fully functional as a result of the restoration of their proliferative capacity."
However, since telomerase is known to be produced at higher rates in cancer cells, there are some safety concerns that remain.
But on the positive side, when scientists added TAT2 to tumor cells they found it did not affect the amount of telomerase produced by those cells. Furthermore, it produced no changes in the growth characteristics of immune cells that were incubated with a virus that can trigger cancer.
"We are fairly confident at this point that TAT2 won't enhance cancer development," Effros said, adding that she has increased confidence by the fact that Astragalus has been used without adverse effects in Chinese medicine. However, she cautions that further trials are needed to confirm the results, and warns against taking large doses of Astragalus to attempt to replicate the TAT2 effect.
"Uncontrolled use of any herbal drug is not wise and I would not advocate it," she said.
Effros and de Grey believe TAT2 might also find applications in other diseases and in general ageing. For instance, killer T-cells fight many viruses besides HIV, and often enter into a state of anergy, in which they stop dividing but won't die, in the elderly.
"One can envision perhaps improving the vaccine response and other anti-viral responses in the elderly by TAT2," said Effros, referring to vaccine responses among the elderly that seem to correlate with high numbers of killer T-cells with short telomeres.
In reference to TAT 2 applications for more general tissue regeneration, she said: "if TAT2 can do what the telomerase gene seems to do by keeping cells growing and functioning longer, maybe it could help in tissue regeneration approaches to ageing."
The study was published in the Journal of Immunology.
Image 1: Telomere caps. Telomeres are believed to affect the lifespan of cells. Courtesy U.S. Department of Energy Human Genome Program.
Image 2: Electron microscopic image of a single human "killer" T-cell (Image: US National Cancer Institute)
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