Individual cells keep track of
generations with the length of their chromosome tails. Every
chromosome has a tail, called a telomere ,
and the telomere gets shorter each time the cell divides. It
has been known since the 1960s that short telomeres can make a cell
act old and tired. Cells with really short telomeres stop growing
and dividing altogether.
Cells get a new lease on life from an
enzyme called telomerase .
Telomerase lengthens the tail of the chromosome. Every cell has the
gene to make telomerase, but curiously, most cells don't use it
most of the time. The telomere is allowed to get shorter with each
generation of cells. In animals, it is normal for telomeres to get
shorter and shorter over the animal's life span. Telomerase is
activated only during reproduction, so that each embryo is provided
with full-length telomeres at the start of life.
So older people tend to have shorter
telomeres than younger people. For a long while, it was thought that
this is an aging mechanism for individual cells
only, and it probably has little relationship to the way a whole
animal ages. In 1996, Stanford professor Michael Fossel published a
that set forth the idea that human aging had a lot to do with
telomere length, and that aging might be slowed or reversed if
therapies could be developed to lengthen the telomeres in our cells.
Most biologists were skeptical. That would be too easy, they
thought. After all, the body knows very well how to restore the
telomere's length. If staying young was as easy as bringing out
the telomerase, why wouldn't the body do it routinely?
surprise came in 2003. A study was done of 60-year-old people, checking the length of the telomeres in their
blood cells. There is natural variation among people in the length
of their telomeres, even at the same age. The surprise was that
people with the shortest telomeres were dying at twice the
rate of those with the longest
telomeres at the same age. Scientists began to believe Fossel's
idea: that telomere length must
have a lot to do with human aging. The race was on to find drugs or
other ways to induce the body to use its own supply of telomerase.
The pioneer was Geron Corp. There are at least five companies working on this problem. The
current leader is Sierra Sciences.
Some biologists think that it can't be so easy. If the body isn't making telomerase on its own, there must be a reason. Most cancer cells manufacture telomerase, so they theorize that perhaps extending telomeres will lead to cancer, and actually shorten life span. But medical evidence seems to point in the other direction. People with short telomeres have higher cancer risk, not lower. Cells with short telomeres send out signals that cause inflammation, and elevate risk for cancer as well as heart disease, diabetes, and dementia.
Geron discovered a drug -- actually an extract from an ancient Chinese herb -- that encourages cells to bring telomerase out of the closet. First in cell cultures and then in lab animals, they found that the extract is associated with lengthening of telomeres. In 2004, a New York company called TA Sciences bought the rights from Geron for a secret formulation that they began to market under the name TA-65, charging up to $20,000 per year for treatments. They had few takers at that price, and in 2010 they published a detailed report on their first 13 clients. With so few people over just three years, it was difficult to extract the signal from the noise. The best they were able to show was that the number of cells with very short telomeres was reduced. This could be important because these are the bad actors, the cells that send out pro-inflammatory signals.
In 2011, independent scientists bought a sample of TA-65 and subjected it to analysis. They reported that the active ingredients are cycloastragenol and, to a lesser extent, astrageloside IV. A Chinese pharmaceutical company began to manufacture supplements with these substances, and market them in the West under the trade names CrackAging and Astraglaxo. You can buy capsules from Amazon.com., still expensive but nowhere near $20,000 a year.
There is one study of TA-65 in mice, by a lab in Spain that has been prominent in anti-aging research. Mice that are fed TA-65 were shown to be healthier and have longer telomeres. They did not get cancer more frequently than other mice, but they also did not live longer on average. The daily dosage that the mice received was 25 mg per kg of body weight. The human equivalent would be about 60 capsules daily of the largest size available from CrackAging. That's $250 per day at current prices.
There is one reason to expect TA-65 might work better in humans: mice already have extra-long telomeres, and it might be that human life span is limited by telomere length to a much greater extent than in mice.
Other much more common supplements have been shown to have small but measurable effect in stimulating the activity of telomerase: The amino acid carnosine which is sold as a nutritional supplement may stimulate the body to express telomerase. Omega-3 fatty acids (from fish oil) have also been suggested as an aid in maintaining telomere length. Stress management and even meditation have measurable effects. It may be that curcumin and resveratrol have small benefits for telomerase expression. A major research effort is coming out of the lab under Elizabeth Blackburn at UCSF, who was the first to discover telomerase, and won a Nobel prize.
The bottom line: Telomere extension shows great promise as an anti-aging therapy. Cyclo-astragenol might be the best treatment currently available, though it is expensive and not as potent as we would like. Data about telomerase and life extension is still preliminary.