Electron microscopic image of a single human “killer” T-cell (Image: US National Cancer Institute)

A drug extracted from a plant used in Chinese medicine has helped immune cells fight HIV and raises the possibility of slowing the ageing process in other parts of our bodies.

The method hinges upon telomeres – caps of repetitive DNA found at the ends of chromosomes. These get shorter as cells age and are thought to affect the cell’s lifespan.

The caps can be rebuilt with an enzyme called telomerase, and some people have suggested it might be possible to extend human life by boosting telomerase production – though this has never been tested.


Now Rita Effros at the University of California in Los Angeles has used a drug that boosts telomerase to enhance the immune response to viruses.

Effros and her colleagues had previously inserted part of the telomerase gene into so-called killer T-cells – immune cells that fight infections including HIV – and found that the cells had stronger anti-viral activity than normal. However, such gene therapy is not a practical way of treating the millions of people infected with HIV.

In the latest work, Effros took killer T-cells from HIV-infected people and exposed them to TAT2. Developed by Geron Corporation of Menlo Park, California, TAT2 is a drug extracted from the root of a plant called Astragalus that is thought to boost telomerase production and is traditionally used in Chinese medicine as a boost for the immune system.

She found that TAT2 reduced telomere shortening, increased cells’ ability to divide, and enhanced their antiviral activity.

This effect was blocked when a second drug was used to inhibit telomerase, suggesting that TAT2 was indeed working through the enzyme – although the exact mechanism is not understood.

Immune boost

“It is beginning to look like telomerase is doing more than just keeping telomeres from getting too short,” says Effros. “It seems to be mediating some anti-viral mechanisms as well.”

Interestingly, a previous study suggested that people with HIV who control the infection for many years without developing AIDS, have killer T-cells with high telomerase activity and longer telomeres.

Ultimately, Effros hopes that TAT2 could be used to supplement existing anti-retroviral drugs, by boosting the immune systems of people with HIV.

Aubrey de Grey of the Methuselah Foundation, which promotes research into lifespan extension, says the study is a big step forward.

“It is what we would have hoped,” he says. “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, some safety concerns remain, as telomerase is known to be produced at higher than normal rates in cancer cells.

Low cancer risk

The good news is that when TAT2 was added to tumour cells it didn’t affect the amount of telomerase that was produced by the cells. Neither did it change 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,” says Effros, although she cautions that further trials are needed to confirm this.

Her confidence is also boosted by the fact that Astragalus is used in Chinese medicine without any obvious adverse effects. She warns, though, against taking large doses of Astragalus to try and mimic the TAT2 effect. “Uncontrolled use of any herbal drug is not wise and I would not advocate it,” she says.

Effros and de Grey believe that TAT2 could also find applications in other diseases and general ageing – though these have not yet been tested. Killer T-cells fight many other viruses besides HIV, and often enter into a state of anergy – where they stop dividing but won’t die – in elderly people. Since response to flu vaccine in elderly people seems to be correlated with having lots of killer T-cells with short telomeres, “One can envision perhaps improving the vaccine response and other anti-viral responses in the elderly by TAT2,” says Effros.

And in terms of more general tissue regeneration, “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.”

Journal reference: The Journal of Immunology (vol 181, p 7400)